12-128414894-C-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

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62
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 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
TMEM132CNM_001136103.3 linkc.248C>A p.Ser83Tyr missense_variant Exon 2 of 9 ENST00000435159.3 NP_001129575.2 Q8N3T6
TMEM132CNM_001387058.1 linkc.188C>A p.Ser63Tyr missense_variant Exon 2 of 9 NP_001373987.1
TMEM132CXM_047429886.1 linkc.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
TMEM132CENST00000435159.3 linkc.248C>A p.Ser83Tyr missense_variant Exon 2 of 9 5 NM_001136103.3 ENSP00000410852.2 Q8N3T6

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
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:
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
LINK: link

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; API