X-154348732-G-A

Position:

• chrX-154348732-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001110556.2(FLNA):​c.*117C>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 0.006 in 653,514 control chromosomes in the GnomAD database, including 120 homozygotes. There are 1,004 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (80 hom., 663 hem., cov: 24)
  • Exomes 𝑓: 0.0027 (40 hom. 341 hem.)
• Consequence: FLNA NM_001110556.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.360

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-154348732-G-A is Benign according to our data. Variant chrX-154348732-G-A is described in ClinVar as [Benign]. Clinvar id is 1242239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLNA	NM_001110556.2	c.*117C>T		3_prime_UTR_variant	48/48	ENST00000369850.10	NP_001104026.1
FLNA	NM_001456.4	c.*117C>T		3_prime_UTR_variant	47/47		NP_001447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLNA	ENST00000369850.10	c.*117C>T		3_prime_UTR_variant	48/48	1	NM_001110556.2	ENSP00000358866

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 2455 AN: 110218 Hom.: 80 Cov.: 24 AF XY: 0.0203 AC XY: 660 AN XY: 32458

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00677

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.000247

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.00268 AC: 1457 AN: 543251 Hom.: 40 Cov.: 8 AF XY: 0.00228 AC XY: 341 AN XY: 149643

Gnomad4 AFR exome AF: 0.0777

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000884

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000250

Gnomad4 OTH exome AF: 0.00582

GnomAD4 genome AF: 0.0223 AC: 2461 AN: 110263 Hom.: 80 Cov.: 24 AF XY: 0.0204 AC XY: 663 AN XY: 32513

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.00676

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000247

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0167 Hom.: 56

Bravo AF: 0.0255

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.5
DANN	Benign	0.75
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.5

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: rs149379012; hg19: chrX-153577100;