Variant 12-128414923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001136103.3(TMEM132C):c.277C>T(p.Pro93Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM132C
NM_001136103.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

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]

TMEM132C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132C	NM_001136103.3 linkuse as main transcript	c.277C>T	p.Pro93Ser	missense_variant	2/9	ENST00000435159.3	NP_001129575.2	Q8N3T6
TMEM132C	NM_001387058.1 linkuse as main transcript	c.217C>T	p.Pro73Ser	missense_variant	2/9		NP_001373987.1
TMEM132C	XM_047429886.1 linkuse as main transcript	c.277C>T	p.Pro93Ser	missense_variant	2/9		XP_047285842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132C	ENST00000435159.3 linkuse as main transcript	c.277C>T	p.Pro93Ser	missense_variant	2/9	5	NM_001136103.3	ENSP00000410852.2		Q8N3T6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000644

AC:

AN:

155296

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.277C>T (p.P93S) alteration is located in exon 2 (coding exon 2) of the TMEM132C gene. This alteration results from a C to T substitution at nucleotide position 277, causing the proline (P) at amino acid position 93 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.4

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0080

Vest4

0.85

MutPred

0.54

Loss of catalytic residue at P92 (P = 0.016);

MVP

0.53

MPC

0.49

ClinPred

0.97

GERP RS

4.4

Varity_R

0.37

gMVP

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over