Variant X-132077056-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.246

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 (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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
FRMD7	NM_194277.3 linkuse as main transcript	c.*816G>A		3_prime_UTR_variant	12/12	ENST00000298542.9	NP_919253.1	Q6ZUT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD7	ENST00000298542 linkuse as main transcript	c.*816G>A		3_prime_UTR_variant	12/12	1	NM_194277.3	ENSP00000298542.3		Q6ZUT3-1
FRMD7	ENST00000370879 linkuse as main transcript	c.*816G>A		3_prime_UTR_variant	8/8	1		ENSP00000359916.1		X6R7S7

Frequencies

GnomAD3 genomes

AF:

0.0896

AC:

9974

AN:

111316

Hom.:

387

Cov.:

AF XY:

0.0848

AC XY:

2850

AN XY:

33590

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.0896

AC:

9983

AN:

111370

Hom.:

387

Cov.:

AF XY:

0.0850

AC XY:

2860

AN XY:

33654

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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