chr2-97757374-C-T

Variant summary

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

The NM_015348.2(TMEM131):​c.5377G>A​(p.Gly1793Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000344 in 1,597,708 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

TMEM131
NM_015348.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01
Variant links:
Genes affected
TMEM131 (HGNC:30366): (transmembrane protein 131) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1951131).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM131NM_015348.2 linkc.5377G>A p.Gly1793Ser missense_variant Exon 41 of 41 ENST00000186436.10 NP_056163.1 Q92545

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM131ENST00000186436.10 linkc.5377G>A p.Gly1793Ser missense_variant Exon 41 of 41 5 NM_015348.2 ENSP00000186436.5 Q92545
TMEM131ENST00000485245.2 linkn.6435G>A non_coding_transcript_exon_variant Exon 2 of 2 1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152088
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000458
AC:
11
AN:
240176
Hom.:
0
AF XY:
0.0000539
AC XY:
7
AN XY:
129984
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000109
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000346
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000736
Gnomad OTH exome
AF:
0.000173
GnomAD4 exome
AF:
0.0000360
AC:
52
AN:
1445620
Hom.:
0
Cov.:
30
AF XY:
0.0000363
AC XY:
26
AN XY:
716482
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000394
Gnomad4 EAS exome
AF:
0.0000508
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.0000189
Gnomad4 NFE exome
AF:
0.0000427
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152088
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000683
Hom.:
0
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000119
AC:
1
ExAC
AF:
0.0000578
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5377G>A (p.G1793S) alteration is located in exon 41 (coding exon 41) of the TMEM131 gene. This alteration results from a G to A substitution at nucleotide position 5377, causing the glycine (G) at amino acid position 1793 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
0.14
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.63
N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.22
Sift
Benign
0.048
D
Sift4G
Benign
0.20
T
Polyphen
1.0
D
Vest4
0.28
MVP
0.12
MPC
0.23
ClinPred
0.37
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371553887; hg19: chr2-98373837; API