Variant 6-168060954-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024919.6(FRMD1):c.1149C>A(p.His383Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,613,392 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 10 hom., cov: 33)

Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

FRMD1
NM_024919.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

FRMD1 (HGNC:21240): (FERM domain containing 1) Predicted to be involved in positive regulation of hippo signaling. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasmic side of apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FRMD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043929815).

BP6

Variant 6-168060954-G-T is Benign according to our data. Variant chr6-168060954-G-T is described in ClinVar as [Benign]. Clinvar id is 775244.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD1	NM_024919.6 linkuse as main transcript	c.1149C>A	p.His383Gln	missense_variant	9/11	ENST00000283309.11	NP_079195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD1	ENST00000283309.11 linkuse as main transcript	c.1149C>A	p.His383Gln	missense_variant	9/11	1	NM_024919.6	ENSP00000283309		Q8N878-1

Frequencies

GnomAD3 genomes

AF:

0.00828

AC:

1260

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00845

AC:

2113

AN:

250064

Hom.:

AF XY:

0.00877

AC XY:

1189

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.00254

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00359

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00480

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.00869

GnomAD4 exome

AF:

0.0108

AC:

15738

AN:

1461060

Hom.:

121

Cov.:

AF XY:

0.0106

AC XY:

7669

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00518

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00893

GnomAD4 genome

AF:

0.00826

AC:

1259

AN:

152332

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00245

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00755

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00865

AC:

1050

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.77

DANN

Benign

0.45

DEOGEN2

Benign

0.0049

.;.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.34

T;T;T;T;T

MetaRNN

Benign

0.0044

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.88

.;.;N;N;.

REVEL

Benign

0.017

Sift

Benign

0.50

.;.;T;T;.

Sift4G

Benign

0.094

.;.;T;T;.

Polyphen

0.0010

.;.;B;B;.

Vest4

0.16, 0.13

MutPred

0.20

.;.;Loss of catalytic residue at H383 (P = 0.0555);.;.;

MVP

0.28

MPC

0.10

ClinPred

0.0055

GERP RS

0.15

Varity_R

0.078

gMVP

0.17

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