X-154348761-G-A

Position:

• chrX-154348761-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001110556.2(FLNA):​c.*88C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00897 in 855,097 control chromosomes in the GnomAD database, including 35 homozygotes. There are 2,047 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (0 hom., 196 hem., cov: 23)
  • Exomes 𝑓: 0.0093 (35 hom. 1851 hem.)
• Consequence: FLNA NM_001110556.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.28

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-154348761-G-A is Benign according to our data. Variant chrX-154348761-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1199805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00666 (685/102882) while in subpopulation NFE AF= 0.0105 (533/50741). AF 95% confidence interval is 0.00977. There are 0 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 196 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNA	NM_001110556.2	c.*88C>T		3_prime_UTR_variant	48/48	ENST00000369850.10	NP_001104026.1
FLNA	NM_001456.4	c.*88C>T		3_prime_UTR_variant	47/47		NP_001447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNA	ENST00000369850	c.*88C>T		3_prime_UTR_variant	48/48	1	NM_001110556.2	ENSP00000358866.3

Frequencies

GnomAD3 genomes AF: 0.00666 AC: 685 AN: 102877 Hom.: 0 Cov.: 23 AF XY: 0.00684 AC XY: 196 AN XY: 28661

Gnomad AFR AF: 0.00146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000921

Gnomad ASJ AF: 0.0249

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.00441

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00214

GnomAD4 exome AF: 0.00928 AC: 6981 AN: 752215 Hom.: 35 Cov.: 13 AF XY: 0.00894 AC XY: 1851 AN XY: 207103

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.0000388

Gnomad4 SAS exome AF: 0.00199

Gnomad4 FIN exome AF: 0.00689

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00666 AC: 685 AN: 102882 Hom.: 0 Cov.: 23 AF XY: 0.00683 AC XY: 196 AN XY: 28686

Gnomad4 AFR AF: 0.00146

Gnomad4 AMR AF: 0.000920

Gnomad4 ASJ AF: 0.0249

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.00214

Alfa AF: 0.00594 Hom.: 27

Bravo AF: 0.00526

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.61
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

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

LitVar

Other links and lift over

dbSNP: rs55760624; hg19: chrX-153577129;