rs781910090

Variant names:

• chrX-154351689-G-A
• rs781910090
• NM_001110556.2:c.6915C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-154351689-G-A
• chrX-154351689-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001110556.2(FLNA):​c.6915C>T​(p.Tyr2305Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,070,184 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000010 (0 hom. 7 hem.)
• Consequence: FLNA NM_001110556.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.335

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant X-154351689-G-A is Benign according to our data. Variant chrX-154351689-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1625570.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.335 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 7 AR,XLR,XLD,XL,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNA	NM_001110556.2	c.6915C>T	p.Tyr2305Tyr	synonymous_variant	Exon 43 of 48	ENST00000369850.10	NP_001104026.1
FLNA	NM_001456.4	c.6891C>T	p.Tyr2297Tyr	synonymous_variant	Exon 42 of 47		NP_001447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNA	ENST00000369850.10	c.6915C>T	p.Tyr2305Tyr	synonymous_variant	Exon 43 of 48	1	NM_001110556.2	ENSP00000358866.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000166 AC: 3 AN: 180393 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 11 AN: 1070184 Hom.: 0 Cov.: 28 AF XY: 0.0000207 AC XY: 7 AN XY: 338266

African (AFR) AF: 0.0000386 AC: 1 AN: 25905

American (AMR) AF: 0.00 AC: 0 AN: 35169

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19244

East Asian (EAS) AF: 0.00 AC: 0 AN: 30106

South Asian (SAS) AF: 0.000112 AC: 6 AN: 53503

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40135

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4072

European-Non Finnish (NFE) AF: 0.00000367 AC: 3 AN: 816889

Other (OTH) AF: 0.0000221 AC: 1 AN: 45161

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Thrombocytopenia Uncertain:1

-

ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1

Sep 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Apr 17, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.3
DANN	Benign	0.47
PhyloP100		-0.34
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=98/2	polymorphism

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

Loading publications...

Other links and lift over

dbSNP: rs781910090; hg19: chrX-153580057;