12-128414894-C-A

Variant names:

• chr12-128414894-C-A
• NM_001136103.3:c.248C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136103.3(TMEM132C):​c.248C>A​(p.Ser83Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM132C NM_001136103.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132C	NM_001136103.3	c.248C>A	p.Ser83Tyr	missense_variant	Exon 2 of 9	ENST00000435159.3	NP_001129575.2
TMEM132C	NM_001387058.1	c.188C>A	p.Ser63Tyr	missense_variant	Exon 2 of 9		NP_001373987.1
TMEM132C	XM_047429886.1	c.248C>A	p.Ser83Tyr	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.248C>A	p.Ser83Tyr	missense_variant	Exon 2 of 9	5	NM_001136103.3	ENSP00000410852.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399632 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690350

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: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248C>A (p.S83Y) alteration is located in exon 2 (coding exon 2) of the TMEM132C gene. This alteration results from a C to A substitution at nucleotide position 248, causing the serine (S) at amino acid position 83 to be replaced by a tyrosine (Y). 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	0.18
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.15
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0050	D
Vest4		0.57
MVP		0.12
MPC		0.18
ClinPred		0.85	D
GERP RS		4.3
Varity_R		0.25
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-128899439;