12-128414785-C-G

Variant names:

• chr12-128414785-C-G
• rs765415062
• NM_001136103.3:c.139C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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 𝑓: 7.2e-7 (0 hom.)
• Consequence: TMEM132C NM_001136103.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

Genes affected

TMEM132C (HGNC:25436): (transmembrane protein 132C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
TMEM132C	NM_001136103.3	c.139C>G	p.Pro47Ala	missense_variant	Exon 2 of 9	ENST00000435159.3	NP_001129575.2
TMEM132C	NM_001387058.1	c.79C>G	p.Pro27Ala	missense_variant	Exon 2 of 9		NP_001373987.1
TMEM132C	XM_047429886.1	c.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
TMEM132C	ENST00000435159.3	c.139C>G	p.Pro47Ala	missense_variant	Exon 2 of 9	5	NM_001136103.3	ENSP00000410852.2

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

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

Other links and lift over

dbSNP: rs765415062; hg19: chr12-128899330;