Variant chrX-132077272-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_194277.3(FRMD7):c.*600C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 111,901 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 79 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., 79 hem., cov: 23)

Exomes 𝑓: 0.0029 ( 0 hom. 0 hem. )

Consequence

FRMD7
NM_194277.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.314

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00293 (327/111562) while in subpopulation NFE AF= 0.00501 (266/53041). AF 95% confidence interval is 0.00452. There are 0 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Hemizygotes in GnomAd4 at 79 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD7	NM_194277.3 linkuse as main transcript	c.*600C>G		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.*600C>G		3_prime_UTR_variant	12/12	1	NM_194277.3	ENSP00000298542.3		Q6ZUT3-1
FRMD7	ENST00000370879 linkuse as main transcript	c.*600C>G		3_prime_UTR_variant	8/8	1		ENSP00000359916.1		X6R7S7

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

327

AN:

111510

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

AN XY:

33720

show subpopulations

Gnomad AFR

AF:

0.000782

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00134

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00133

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.000668

GnomAD4 exome

AF:

0.00295

AC:

AN:

339

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00403

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00293

AC:

327

AN:

111562

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

AN XY:

33782

show subpopulations

Gnomad4 AFR

AF:

0.000781

Gnomad4 AMR

AF:

0.00134

Gnomad4 ASJ

AF:

0.00492

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00133

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.000659

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00281

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nystagmus 1, congenital, X-linked

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.72

DANN

Benign

0.85

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