rs6637934

Positions:

chrX-132078614-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_194277.3(FRMD7):c.1403G>A(p.Arg468His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,208,945 control chromosomes in the GnomAD database, including 1,507 homozygotes. There are 22,909 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 158 hom., 1835 hem., cov: 22)

Exomes 𝑓: 0.058 ( 1349 hom. 21074 hem. )

Consequence

FRMD7
NM_194277.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.418

Variant links:

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]

FRMD7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013616383).

BP6

Variant X-132078614-C-T is Benign according to our data. Variant chrX-132078614-C-T is described in ClinVar as [Benign]. Clinvar id is 263087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-132078614-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD7	NM_194277.3 linkuse as main transcript	c.1403G>A	p.Arg468His	missense_variant	12/12	ENST00000298542.9	NP_919253.1	Q6ZUT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FRMD7	ENST00000298542.9 linkuse as main transcript	c.1403G>A	p.Arg468His	missense_variant	12/12	1	NM_194277.3	ENSP00000298542.3	Q6ZUT3-1
FRMD7	ENST00000464296.1 linkuse as main transcript	c.1358G>A	p.Arg453His	missense_variant	12/12	1		ENSP00000417996.1	Q6ZUT3-2
FRMD7	ENST00000370879.5 linkuse as main transcript	c.1043G>A	p.Arg348His	missense_variant	8/8	1		ENSP00000359916.1	X6R7S7

Frequencies

GnomAD3 genomes

AF:

0.0588

AC:

6567

AN:

111629

Hom.:

156

Cov.:

AF XY:

0.0541

AC XY:

1831

AN XY:

33843

show subpopulations

Gnomad AFR

AF:

0.0733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0950

Gnomad EAS

AF:

0.0982

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.0366

Gnomad MID

AF:

0.0591

Gnomad NFE

AF:

0.0558

Gnomad OTH

AF:

0.0498

GnomAD3 exomes

AF:

0.0562

AC:

10268

AN:

182862

Hom.:

196

AF XY:

0.0582

AC XY:

3935

AN XY:

67562

show subpopulations

Gnomad AFR exome

AF:

0.0757

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0778

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.0664

Gnomad FIN exome

AF:

0.0450

Gnomad NFE exome

AF:

0.0565

Gnomad OTH exome

AF:

0.0598

GnomAD4 exome

AF:

0.0580

AC:

63652

AN:

1097261

Hom.:

1349

Cov.:

AF XY:

0.0581

AC XY:

21074

AN XY:

362653

show subpopulations

Gnomad4 AFR exome

AF:

0.0791

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.0795

Gnomad4 EAS exome

AF:

0.0732

Gnomad4 SAS exome

AF:

0.0690

Gnomad4 FIN exome

AF:

0.0452

Gnomad4 NFE exome

AF:

0.0574

Gnomad4 OTH exome

AF:

0.0651

GnomAD4 genome

AF:

0.0588

AC:

6568

AN:

111684

Hom.:

158

Cov.:

AF XY:

0.0541

AC XY:

1835

AN XY:

33908

show subpopulations

Gnomad4 AFR

AF:

0.0734

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0950

Gnomad4 EAS

AF:

0.0969

Gnomad4 SAS

AF:

0.0716

Gnomad4 FIN

AF:

0.0366

Gnomad4 NFE

AF:

0.0558

Gnomad4 OTH

AF:

0.0492

Alfa

AF:

0.0583

Hom.:

4396

Bravo

AF:

0.0583

TwinsUK

AF:

0.0636

AC:

236

ALSPAC

AF:

0.0613

AC:

177

ESP6500AA

AF:

0.0754

AC:

289

ESP6500EA

AF:

0.0572

AC:

385

ExAC

AF:

0.0594

AC:

7216

EpiCase

AF:

0.0554

EpiControl

AF:

0.0567

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nystagmus 1, congenital, X-linked

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

.;T;.

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

1.3

N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.64, 0.75

.;P;P

Vest4

0.028

MPC

0.36

ClinPred

0.017

GERP RS

4.9

Varity_R

0.14

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over