Variant X-132077872-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2

The NM_194277.3(FRMD7):c.2145A>T(p.Ter715Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,209,613 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.000080 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

FRMD7
NM_194277.3 stop_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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 Likely_benign. Variant got -2 ACMG points.

PM4

Stoplost variant in NM_194277.3 Downstream stopcodon found after 364 codons.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD7	NM_194277.3 linkuse as main transcript	c.2145A>T	p.Ter715Tyrext*?	stop_lost	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.2145A>T	p.Ter715Tyrext*?	stop_lost	12/12	1	NM_194277.3	ENSP00000298542.3	Q6ZUT3-1
FRMD7	ENST00000370879.5 linkuse as main transcript	c.1785A>T	p.Ter595Tyrext*?	stop_lost	8/8	1		ENSP00000359916.1	X6R7S7
FRMD7	ENST00000464296.1 linkuse as main transcript	c.2100A>T	p.Ter700Tyrext*?	stop_lost, splice_region_variant	12/12	1		ENSP00000417996.1	Q6ZUT3-2

Frequencies

GnomAD3 genomes

AF:

0.0000800

AC:

AN:

112467

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

34615

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182790

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67480

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1097146

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362566

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000800

AC:

AN:

112467

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

34615

show subpopulations

Gnomad4 AFR

AF:

0.000291

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1008913). This variant has not been reported in the literature in individuals affected with FRMD7-related conditions. This variant is present in population databases (rs372458379, gnomAD 0.01%). This sequence change disrupts the translational stop signal of the FRMD7 mRNA. It is expected to extend the length of the FRMD7 protein by 24 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.24

CADD

Benign

6.9

DANN

Benign

0.81

FATHMM_MKL

Uncertain

0.89

Vest4

0.17

GERP RS

3.4

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