9-83290671-T-C

Variant summary

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

The NM_174938.6(FRMD3):​c.1127A>G​(p.Asn376Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000287 in 1,461,688 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: 0.000029 ( 0 hom. )

Consequence

FRMD3
NM_174938.6 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.52

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]

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=0.24452898).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRMD3NM_174938.6 linkc.1127A>G p.Asn376Ser missense_variant Exon 13 of 14 ENST00000304195.8 NP_777598.3 A2A2Y4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRMD3ENST00000304195.8 linkc.1127A>G p.Asn376Ser missense_variant Exon 13 of 14 1 NM_174938.6 ENSP00000303508.3 A2A2Y4-1
FRMD3ENST00000621208.4 linkc.995A>G p.Asn332Ser missense_variant Exon 13 of 14 1 ENSP00000484839.1 A2A2Y4-5
FRMD3ENST00000376434.5 linkc.545A>G p.Asn182Ser missense_variant Exon 8 of 10 1 ENSP00000365617.1 A2A2Y4-3
FRMD3ENST00000376438.5 linkc.1127A>G p.Asn376Ser missense_variant Exon 13 of 15 2 ENSP00000365621.1 A2A2Y4-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.0000161
AC:
4
AN:
249136
AF XY:
0.00000740
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:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461688
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727150
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26116
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.0000369
AC:
41
AN:
1111904
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.461
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
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
Nov 10, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1127A>G (p.N376S) 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 1127, causing the asparagine (N) at amino acid position 376 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0082
.;.;T;.
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Benign
1.8
.;L;L;.
PhyloP100
6.5
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.91
N;N;N;.
REVEL
Uncertain
0.38
Sift
Benign
0.24
T;T;T;.
Sift4G
Benign
0.69
T;T;T;T
Polyphen
0.89, 0.90
.;P;P;.
Vest4
0.36
MVP
0.75
MPC
0.63
ClinPred
0.47
T
GERP RS
5.9
Varity_R
0.15
gMVP
0.35
Mutation Taster
=65/35
polymorphism

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

Other links and lift over

dbSNP: rs754732127; hg19: chr9-85905586; API