Genetic Variant FRMD3:p.Arg364Gly (chr9-83290708-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_174938.6(FRMD3):c.1090C>G(p.Arg364Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R364C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FRMD3
NM_174938.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

0 publications found

Variant links:

Genes affected

FRMD3 (HGNC:24125): (FERM domain containing 3) The protein encoded by this gene is a single pass membrane protein primarily found in ovaries. A similar protein in erythrocytes helps determine the shape of red blood cells, but the function of the encoded protein has not been determined. There is some evidence that this is a tumor suppressor gene, and there is also evidence linking defects in this gene to susceptibility to diabetic nephropathy in type 1 diabetes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

FRMD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6 link	c.1090C>G	p.Arg364Gly	missense_variant	Exon 13 of 14	ENST00000304195.8	NP_777598.3	A2A2Y4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FRMD3	ENST00000304195.8 link	c.1090C>G	p.Arg364Gly	missense_variant	Exon 13 of 14	1	NM_174938.6	ENSP00000303508.3	A2A2Y4-1
FRMD3	ENST00000621208.4 link	c.958C>G	p.Arg320Gly	missense_variant	Exon 13 of 14	1		ENSP00000484839.1	A2A2Y4-5
FRMD3	ENST00000376434.5 link	c.508C>G	p.Arg170Gly	missense_variant	Exon 8 of 10	1		ENSP00000365617.1	A2A2Y4-3
FRMD3	ENST00000376438.5 link	c.1090C>G	p.Arg364Gly	missense_variant	Exon 13 of 15	2		ENSP00000365621.1	A2A2Y4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460046

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111030

Other (OTH)

AF:

0.00

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

.;.;D;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

1.7

.;L;L;.

PhyloP100

2.0

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.3

D;D;D;.

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0010

D;D;D;.

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.80, 0.81

.;P;P;.

Vest4

0.73

MutPred

0.56

.;Loss of MoRF binding (P = 0.0068);Loss of MoRF binding (P = 0.0068);.;

MVP

0.76

MPC

0.37

ClinPred

0.99

GERP RS

3.9

Varity_R

0.59

gMVP

0.59

Mutation Taster

=64/36

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.

9-83290708-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over