12-128439181-A-G

Position:

• chr12-128439181-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.974+23561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 164,750 control chromosomes in the GnomAD database, including 9,089 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 0.31 (7920 hom., cov: 31)
  • Exomes 𝑓: 0.43 (1169 hom.)
• Consequence: TMEM132C NM_001136103.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

Genes affected

TMEM132C (HGNC:25436): (transmembrane protein 132C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256630 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132C	NM_001136103.3	c.974+23561A>G		intron_variant		ENST00000435159.3	NP_001129575.2
TMEM132C	NM_001387058.1	c.914+23561A>G		intron_variant			NP_001373987.1
TMEM132C	XM_047429886.1	c.974+23561A>G		intron_variant			XP_047285842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132C	ENST00000435159.3	c.974+23561A>G		intron_variant		5	NM_001136103.3	ENSP00000410852.2
ENSG00000256630	ENST00000535243.1	n.26T>C		non_coding_transcript_exon_variant	1/2	6

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47860 AN: 151888 Hom.: 7920 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.431 AC: 5499 AN: 12744 Hom.: 1169 Cov.: 0 AF XY: 0.440 AC XY: 3380 AN XY: 7686

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.597

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.315 AC: 47877 AN: 152006 Hom.: 7920 Cov.: 31 AF XY: 0.320 AC XY: 23768 AN XY: 74310

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.300

Alfa AF: 0.314 Hom.: 10133

Bravo AF: 0.296

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.99
DANN	Benign	0.46

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: rs10773543; hg19: chr12-128923726;