rs2220486

Positions:

• chr12-128607596-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136103.3(TMEM132C):​c.1122-8556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,022 control chromosomes in the GnomAD database, including 35,509 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 0.68 (35509 hom., cov: 32)
• Consequence: TMEM132C NM_001136103.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132C	NM_001136103.3	c.1122-8556A>G		intron_variant		ENST00000435159.3	NP_001129575.2
TMEM132C	NM_001387058.1	c.1062-8556A>G		intron_variant			NP_001373987.1
TMEM132C	XM_047429886.1	c.1122-8556A>G		intron_variant			XP_047285842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132C	ENST00000435159.3	c.1122-8556A>G		intron_variant		5	NM_001136103.3	ENSP00000410852	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103489 AN: 151904 Hom.: 35459 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.681 AC: 103597 AN: 152022 Hom.: 35509 Cov.: 32 AF XY: 0.678 AC XY: 50373 AN XY: 74286

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.695

Alfa AF: 0.683 Hom.: 66337

Bravo AF: 0.689

Asia WGS AF: 0.659 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs2220486; hg19: chr12-129092141; COSMIC: COSV59432476;