X-154348765-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001110556.2(FLNA):c.*84A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 982,339 control chromosomes in the GnomAD database, including 6,645 homozygotes. There are 36,799 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1311 hom., 5235 hem., cov: 24)
  • Exomes 𝑓: 0.13 (5334 hom. 31564 hem.)
• Consequence: FLNA NM_001110556.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.718

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154348765-T-G is Benign according to our data. Variant chrX-154348765-T-G is described in ClinVar as [Benign]. Clinvar id is 1258029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLNA	NM_001110556.2	c.*84A>C		3_prime_UTR_variant	48/48	ENST00000369850.10
FLNA	NM_001456.4	c.*84A>C		3_prime_UTR_variant	47/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLNA	ENST00000369850.10	c.*84A>C		3_prime_UTR_variant	48/48	1	NM_001110556.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 17778 AN: 110890 Hom.: 1306 Cov.: 24 AF XY: 0.157 AC XY: 5203 AN XY: 33242

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.00295

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0540

Gnomad EAS AF: 0.0573

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0515

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.126 AC: 109371 AN: 871402 Hom.: 5334 Cov.: 14 AF XY: 0.131 AC XY: 31564 AN XY: 240428

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.0596

Gnomad4 EAS exome AF: 0.0706

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.161 AC: 17819 AN: 110937 Hom.: 1311 Cov.: 24 AF XY: 0.157 AC XY: 5235 AN XY: 33299

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0540

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0396 Hom.: 146

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.7
Dann	Benign	0.48

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: rs782243311; hg19: chrX-153577133;