X-132078484-A-G

Position:

chrX-132078484-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_194277.3(FRMD7):c.1533T>C(p.Ile511=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,207,818 control chromosomes in the GnomAD database, including 37,254 homozygotes. There are 114,136 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 4446 hom., 9557 hem., cov: 22)

Exomes 𝑓: 0.29 ( 32808 hom. 104579 hem. )

Consequence

FRMD7
NM_194277.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.390

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant X-132078484-A-G is Benign according to our data. Variant chrX-132078484-A-G is described in ClinVar as [Benign]. Clinvar id is 263088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-132078484-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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.1533T>C	p.Ile511=	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 linkuse as main transcript	c.1533T>C	p.Ile511=	synonymous_variant	12/12	1	NM_194277.3	ENSP00000298542	P1	Q6ZUT3-1
FRMD7	ENST00000464296.1 linkuse as main transcript	c.1488T>C	p.Ile496=	synonymous_variant	12/12	1		ENSP00000417996		Q6ZUT3-2
FRMD7	ENST00000370879.5 linkuse as main transcript	c.1173T>C	p.Ile391=	synonymous_variant	8/8	1		ENSP00000359916

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

34812

AN:

110084

Hom.:

4442

Cov.:

AF XY:

0.294

AC XY:

9523

AN XY:

32370

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.260

AC:

47497

AN:

182804

Hom.:

4504

AF XY:

0.260

AC XY:

17541

AN XY:

67498

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.291

AC:

319158

AN:

1097680

Hom.:

32808

Cov.:

AF XY:

0.288

AC XY:

104579

AN XY:

363080

show subpopulations

Gnomad4 AFR exome

AF:

0.439

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.0736

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.316

AC:

34838

AN:

110138

Hom.:

4446

Cov.:

AF XY:

0.295

AC XY:

9557

AN XY:

32434

show subpopulations

Gnomad4 AFR

AF:

0.428

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.0993

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.299

Hom.:

13460

Bravo

AF:

0.313

EpiCase

AF:

0.305

EpiControl

AF:

0.303

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	-	- -

Nystagmus 1, congenital, X-linked

Benign:2

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. -
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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.68

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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