X-132077056-C-T

Variant summary

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

The NM_194277.3(FRMD7):c.*816G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 111,370 control chromosomes in the GnomAD database, including 387 homozygotes. There are 2,860 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (387 hom., 2860 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: FRMD7 NM_194277.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.246

Genes affected

FRMD7 (HGNC:8079): (FERM domain containing 7) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of neuron projection development. Predicted to act upstream of or within several processes, including negative regulation of stress fiber assembly; positive regulation of lamellipodium assembly; and positive regulation of small GTPase mediated signal transduction. Located in cytosol; nucleoplasm; and plasma membrane. Implicated in congenital nystagmus 1. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-132077056-C-T is Benign according to our data. Variant chrX-132077056-C-T is described in ClinVar as [Benign]. Clinvar id is 367898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD7	NM_194277.3	c.*816G>A		3_prime_UTR_variant	12/12	ENST00000298542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD7	ENST00000298542.9	c.*816G>A		3_prime_UTR_variant	12/12	1	NM_194277.3	P1
FRMD7	ENST00000370879.5	c.*816G>A		3_prime_UTR_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 9974 AN: 111316 Hom.: 387 Cov.: 22 AF XY: 0.0848 AC XY: 2850 AN XY: 33590

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.0572

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0911

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0896 AC: 9983 AN: 111370 Hom.: 387 Cov.: 22 AF XY: 0.0850 AC XY: 2860 AN XY: 33654

Gnomad4 AFR AF: 0.0794

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.0817

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0985 Hom.: 522

Bravo AF: 0.0840

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nystagmus 1, congenital, X-linked Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.9
Dann	Benign	0.58

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: rs41312755; hg19: chrX-131211084;