NM_174938.6:c.1090C>T

Variant names:

Variant summary

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

The NM_174938.6(FRMD3):c.1090C>T(p.Arg364Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

FRMD3
NM_174938.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

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 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>T	p.Arg364Cys	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>T	p.Arg364Cys	missense_variant	Exon 13 of 14	1	NM_174938.6	ENSP00000303508.3	A2A2Y4-1
FRMD3	ENST00000621208.4 link	c.958C>T	p.Arg320Cys	missense_variant	Exon 13 of 14	1		ENSP00000484839.1	A2A2Y4-5
FRMD3	ENST00000376434.5 link	c.508C>T	p.Arg170Cys	missense_variant	Exon 8 of 10	1		ENSP00000365617.1	A2A2Y4-3
FRMD3	ENST00000376438.5 link	c.1090C>T	p.Arg364Cys	missense_variant	Exon 13 of 15	2		ENSP00000365621.1	A2A2Y4-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

247782

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.0000647

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1460046

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726246

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33392

American (AMR)

AF:

0.0000225

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:

0.0000465

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:

0.0000369

AC:

AN:

1111030

Other (OTH)

AF:

0.0000166

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000824

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1090C>T (p.R364C) alteration is located in exon 1 (coding exon 1) of the FRMD3 gene. This alteration results from a C to T substitution at nucleotide position 1090, causing the arginine (R) at amino acid position 364 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.65

.;.;D;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Uncertain

0.33

MutationAssessor

Benign

1.7

.;L;L;.

PhyloP100

2.0

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.1

D;D;D;.

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.38

MutPred

0.61

.;Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);.;

MVP

0.80

MPC

0.24

ClinPred

0.93

GERP RS

3.9

Varity_R

0.50

gMVP

0.51

Mutation Taster

=71/29

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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NM_174938.6:c.1090C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over