9-83248403-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174938.6(FRMD3):​c.1309G>A​(p.Glu437Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FRMD3
NM_174938.6 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2555595).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FRMD3NM_174938.6 linkuse as main transcriptc.1309G>A p.Glu437Lys missense_variant 14/14 ENST00000304195.8 NP_777598.3
FRMD3-AS1NR_184120.1 linkuse as main transcriptn.237+14484C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FRMD3ENST00000304195.8 linkuse as main transcriptc.1309G>A p.Glu437Lys missense_variant 14/141 NM_174938.6 ENSP00000303508 P1A2A2Y4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461878
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 24, 2023The c.1309G>A (p.E437K) alteration is located in exon 1 (coding exon 1) of the FRMD3 gene. This alteration results from a G to A substitution at nucleotide position 1309, causing the glutamic acid (E) at amino acid position 437 to be replaced by a lysine (K). 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
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
.;.;.;T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Uncertain
0.40
D
MutationAssessor
Uncertain
2.1
.;.;M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-2.3
N;N;N;N;.
REVEL
Uncertain
0.44
Sift
Benign
0.040
D;D;D;D;.
Sift4G
Uncertain
0.012
D;T;T;T;T
Polyphen
0.93
P;.;P;P;.
Vest4
0.26
MutPred
0.30
.;.;Gain of ubiquitination at E437 (P = 0.0069);Gain of ubiquitination at E437 (P = 0.0069);.;
MVP
0.79
MPC
0.34
ClinPred
0.89
D
GERP RS
5.7
Varity_R
0.26
gMVP
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-85863318; API