Genetic Variant FRMD1:p.Val467Met (chr6-168059132-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024919.6(FRMD1):c.1399G>A(p.Val467Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,575,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

FRMD1
NM_024919.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.992

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012485385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024919.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FRMD1	NM_024919.6	MANE Select	c.1399G>A	p.Val467Met	missense	Exon 10 of 11	NP_079195.3
FRMD1	NM_001394681.1		c.1204G>A	p.Val402Met	missense	Exon 9 of 10	NP_001381610.1	A0A2R8Y6M2
FRMD1	NM_001122841.3		c.1195G>A	p.Val399Met	missense	Exon 10 of 11	NP_001116313.1	Q8N878-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FRMD1	ENST00000283309.11	TSL:1 MANE Select	c.1399G>A	p.Val467Met	missense	Exon 10 of 11	ENSP00000283309.6	Q8N878-1
FRMD1	ENST00000432403.5	TSL:1	n.1086G>A		non_coding_transcript_exon	Exon 8 of 9
FRMD1	ENST00000646385.1		c.1594G>A	p.Val532Met	missense	Exon 13 of 14	ENSP00000494166.1	A0A2R8Y4L9

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000873

AC:

AN:

194664

AF XY:

0.0000667

show subpopulations

Gnomad AFR exome

AF:

0.000882

Gnomad AMR exome

AF:

0.0000994

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.0000903

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000436

AC:

AN:

1422996

Hom.:

Cov.:

AF XY:

0.0000397

AC XY:

AN XY:

705212

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

33134

American (AMR)

AF:

0.0000977

AC:

AN:

40944

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25584

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38290

South Asian (SAS)

AF:

0.00

AC:

AN:

81522

European-Finnish (FIN)

AF:

0.0000471

AC:

AN:

42446

Middle Eastern (MID)

AF:

0.000192

AC:

AN:

5200

European-Non Finnish (NFE)

AF:

0.00000912

AC:

AN:

1096766

Other (OTH)

AF:

0.0000677

AC:

AN:

59110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000447

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41546

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000392

Hom.:

Bravo

AF:

0.000450

ESP6500AA

AF:

0.00160

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000125

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.7

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.47

M_CAP

Benign

0.0076

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

-0.99

PrimateAI

Benign

0.24

PROVEAN

Benign

0.090

REVEL

Benign

0.019

Sift

Benign

0.057

Sift4G

Benign

0.097

Polyphen

0.064

Vest4

0.061

MVP

0.13

MPC

0.10

ClinPred

0.014

GERP RS

-1.4

Varity_R

0.046

gMVP

0.11

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over