Genetic Variant NM_024919.6:c.1378A>G (chr6-168059153-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024919.6(FRMD1):c.1378A>G(p.Arg460Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRMD1
NM_024919.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.138

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23381132).

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.1378A>G	p.Arg460Gly	missense	Exon 10 of 11	NP_079195.3
FRMD1	NM_001394681.1		c.1183A>G	p.Arg395Gly	missense	Exon 9 of 10	NP_001381610.1	A0A2R8Y6M2
FRMD1	NM_001122841.3		c.1174A>G	p.Arg392Gly	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.1378A>G	p.Arg460Gly	missense	Exon 10 of 11	ENSP00000283309.6	Q8N878-1
FRMD1	ENST00000432403.5	TSL:1	n.1065A>G		non_coding_transcript_exon	Exon 8 of 9
FRMD1	ENST00000646385.1		c.1573A>G	p.Arg525Gly	missense	Exon 13 of 14	ENSP00000494166.1	A0A2R8Y4L9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433938

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711242

African (AFR)

AF:

0.00

AC:

AN:

33250

American (AMR)

AF:

0.00

AC:

AN:

42142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25720

East Asian (EAS)

AF:

0.00

AC:

AN:

38826

South Asian (SAS)

AF:

0.00

AC:

AN:

82466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101874

Other (OTH)

AF:

0.00

AC:

AN:

59434

GnomAD4 genome

Cov.:

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

0.097

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.54

M_CAP

Benign

0.012

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-0.14

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.066

Sift

Uncertain

0.019

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.30

MutPred

0.31

Loss of MoRF binding (P = 0.0394)

MVP

0.66

MPC

0.41

ClinPred

0.83

GERP RS

-1.6

Varity_R

0.16

gMVP

0.22

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over