12-128414785-C-G

Variant summary

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

The NM_001136103.3(TMEM132C):​c.139C>G​(p.Pro47Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000721 in 1,387,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.28
Variant links:
Genes affected
TMEM132C (HGNC:25436): (transmembrane protein 132C) Predicted to be integral component of 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=0.19718948).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM132CNM_001136103.3 linkc.139C>G p.Pro47Ala missense_variant Exon 2 of 9 ENST00000435159.3 NP_001129575.2 Q8N3T6
TMEM132CNM_001387058.1 linkc.79C>G p.Pro27Ala missense_variant Exon 2 of 9 NP_001373987.1
TMEM132CXM_047429886.1 linkc.139C>G p.Pro47Ala missense_variant Exon 2 of 9 XP_047285842.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM132CENST00000435159.3 linkc.139C>G p.Pro47Ala missense_variant Exon 2 of 9 5 NM_001136103.3 ENSP00000410852.2 Q8N3T6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.21e-7
AC:
1
AN:
1387912
Hom.:
0
Cov.:
30
AF XY:
0.00000146
AC XY:
1
AN XY:
684864
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:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
12
DANN
Benign
0.37
DEOGEN2
Benign
0.00059
T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.90
N
REVEL
Benign
0.080
Sift
Benign
0.42
T
Sift4G
Benign
0.49
T
Vest4
0.20
MutPred
0.22
Loss of catalytic residue at P46 (P = 0.0151);
MVP
0.13
MPC
0.10
ClinPred
0.090
T
GERP RS
3.2
Varity_R
0.042
gMVP
0.26

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

LitVar

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

Other links and lift over

dbSNP: rs765415062; hg19: chr12-128899330; API