12-128297477-C-T

Variant names:

• chr12-128297477-C-T
• rs11059635
• NM_001136103.3:c.85+29990C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136103.3(TMEM132C):​c.85+29990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,214 control chromosomes in the GnomAD database, including 787 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.093 (787 hom., cov: 33)
• Consequence: TMEM132C NM_001136103.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM132C	NM_001136103.3	c.85+29990C>T		intron_variant	Intron 1 of 8	ENST00000435159.3	NP_001129575.2
TMEM132C	NM_001387058.1	c.25+29183C>T		intron_variant	Intron 1 of 8		NP_001373987.1
TMEM132C	XM_047429886.1	c.85+29990C>T		intron_variant	Intron 1 of 8		XP_047285842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM132C	ENST00000435159.3	c.85+29990C>T		intron_variant	Intron 1 of 8	5	NM_001136103.3	ENSP00000410852.2

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14081 AN: 152094 Hom.: 784 Cov.: 33

Gnomad AFR AF: 0.0953

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0994

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0925 AC: 14087 AN: 152214 Hom.: 787 Cov.: 33 AF XY: 0.0936 AC XY: 6967 AN XY: 74430

African (AFR) AF: 0.0950 AC: 3947 AN: 41528

American (AMR) AF: 0.0874 AC: 1338 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5164

South Asian (SAS) AF: 0.190 AC: 917 AN: 4824

European-Finnish (FIN) AF: 0.0741 AC: 785 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0806 AC: 5483 AN: 68006

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.0840 Hom.: 2516

Bravo AF: 0.0942

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11059635; hg19: chr12-128782022;