rs7051368

Positions:

• chrX-132078916-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_194277.3(FRMD7):​c.1101T>C​(p.Asn367=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 1,205,850 control chromosomes in the GnomAD database, including 3,561 homozygotes. There are 33,772 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (318 hom., 2541 hem., cov: 22)
  • Exomes 𝑓: 0.089 (3243 hom. 31231 hem.)
• Consequence: FRMD7 NM_194277.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.160

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-132078916-A-G is Benign according to our data. Variant chrX-132078916-A-G is described in ClinVar as [Benign]. Clinvar id is 263086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD7	NM_194277.3	c.1101T>C	p.Asn367=	synonymous_variant	12/12	ENST00000298542.9	NP_919253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD7	ENST00000298542.9	c.1101T>C	p.Asn367=	synonymous_variant	12/12	1	NM_194277.3	ENSP00000298542	P1
FRMD7	ENST00000464296.1	c.1056T>C	p.Asn352=	synonymous_variant	12/12	1		ENSP00000417996
FRMD7	ENST00000370879.5	c.741T>C	p.Asn247=	synonymous_variant	8/8	1		ENSP00000359916

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 9517 AN: 111142 Hom.: 317 Cov.: 22 AF XY: 0.0758 AC XY: 2529 AN XY: 33366

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0523

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.0927

GnomAD3 exomes AF: 0.0688 AC: 12461 AN: 181051 Hom.: 356 AF XY: 0.0666 AC XY: 4464 AN XY: 66987

Gnomad AFR exome AF: 0.0938

Gnomad AMR exome AF: 0.0372

Gnomad ASJ exome AF: 0.0494

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0161

Gnomad FIN exome AF: 0.0836

Gnomad NFE exome AF: 0.0985

Gnomad OTH exome AF: 0.0781

GnomAD4 exome AF: 0.0892 AC: 97648 AN: 1094652 Hom.: 3243 Cov.: 30 AF XY: 0.0867 AC XY: 31231 AN XY: 360286

Gnomad4 AFR exome AF: 0.0980

Gnomad4 AMR exome AF: 0.0399

Gnomad4 ASJ exome AF: 0.0519

Gnomad4 EAS exome AF: 0.0000331

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0841

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0835

GnomAD4 genome AF: 0.0857 AC: 9527 AN: 111198 Hom.: 318 Cov.: 22 AF XY: 0.0760 AC XY: 2541 AN XY: 33432

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.0523

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.0982

Gnomad4 OTH AF: 0.0916

Alfa AF: 0.0920 Hom.: 3609

Bravo AF: 0.0845

EpiCase AF: 0.0990

EpiControl AF: 0.0990

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nystagmus 1, congenital, X-linked Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.68
DANN	Benign	0.63

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: rs7051368; hg19: chrX-131212944; COSMIC: COSV53745461; COSMIC: COSV53745461;