X-154371009-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001110556.2(FLNA):c.237G>A(p.Ala79Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,094,751 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A79A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

FLNA
NM_001110556.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.800

Publications

0 publications found

Variant links:

Genes affected

FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

FLNA Gene-Disease associations (from GenCC):

periventricular nodular heterotopia
Inheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
frontometaphyseal dysplasia 1
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
genetic developmental and epileptic encephalopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
heterotopia, periventricular, X-linked dominant
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Melnick-Needles syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
otopalatodigital syndrome type 2
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
terminal osseous dysplasia-pigmentary defects syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
cardiac valvular dysplasia, X-linked
Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
frontometaphyseal dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital short bowel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
otopalatodigital syndrome type 1
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked Ehlers-Danlos syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
familial thoracic aortic aneurysm and aortic dissection
Inheritance: XL Classification: LIMITED Submitted by: ClinGen

FLNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant X-154371009-C-T is Benign according to our data. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154371009-C-T is described in CliVar as Likely_benign. Clinvar id is 3221694.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.8 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNA	NM_001110556.2 link	c.237G>A	p.Ala79Ala	synonymous_variant	Exon 2 of 48	ENST00000369850.10	NP_001104026.1	P21333-1Q60FE5Q6NXF2
FLNA	NM_001456.4 link	c.237G>A	p.Ala79Ala	synonymous_variant	Exon 2 of 47		NP_001447.2	P21333-2Q60FE5Q6NXF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNA	ENST00000369850.10 link	c.237G>A	p.Ala79Ala	synonymous_variant	Exon 2 of 48	1	NM_001110556.2	ENSP00000358866.3		P21333-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1094751

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360599

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26353

American (AMR)

AF:

0.00

AC:

AN:

34933

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19346

East Asian (EAS)

AF:

0.00

AC:

AN:

30051

South Asian (SAS)

AF:

0.00

AC:

AN:

53639

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39785

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

840550

Other (OTH)

AF:

0.00

AC:

AN:

45963

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Feb 01, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-0.80

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over