chr9-83290720-T-C

Variant names:

Variant summary

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

The NM_174938.6(FRMD3):c.1078A>G(p.Ile360Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,454,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FRMD3
NM_174938.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

Publications

1 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16338566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6 link	c.1078A>G	p.Ile360Val	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.1078A>G	p.Ile360Val	missense_variant	Exon 13 of 14	1	NM_174938.6	ENSP00000303508.3	A2A2Y4-1
FRMD3	ENST00000621208.4 link	c.946A>G	p.Ile316Val	missense_variant	Exon 13 of 14	1		ENSP00000484839.1	A2A2Y4-5
FRMD3	ENST00000376434.5 link	c.496A>G	p.Ile166Val	missense_variant	Exon 8 of 10	1		ENSP00000365617.1	A2A2Y4-3
FRMD3	ENST00000376438.5 link	c.1078A>G	p.Ile360Val	missense_variant	Exon 13 of 15	2		ENSP00000365621.1	A2A2Y4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

243740

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1454814

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

722898

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33182

American (AMR)

AF:

0.00

AC:

AN:

43886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25690

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.00

AC:

AN:

85416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1108022

Other (OTH)

AF:

0.0000166

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1078A>G (p.I360V) alteration is located in exon 1 (coding exon 1) of the FRMD3 gene. This alteration results from a A to G substitution at nucleotide position 1078, causing the isoleucine (I) at amino acid position 360 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;.;T;.

Eigen

Benign

-0.050

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.2

.;L;L;.

PhyloP100

3.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.26

N;N;N;.

REVEL

Uncertain

0.32

Sift

Benign

0.30

T;T;T;.

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.41, 0.30

.;B;B;.

Vest4

0.36

MutPred

0.32

.;Gain of MoRF binding (P = 0.1137);Gain of MoRF binding (P = 0.1137);.;

MVP

0.65

MPC

0.17

ClinPred

0.27

GERP RS

5.9

Varity_R

0.079

gMVP

0.21

Mutation Taster

=86/14

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

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chr9-83290720-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over