chr12-128439181-A-G

Variant names:

• chr12-128439181-A-G
• rs10773543
• NM_001136103.3:c.974+23561A>G

Variant summary

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

The ENST00000435159.3(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 ENST00000435159.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 8 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]

ENSG00000256630 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435159.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132C	NM_001136103.3	MANE Select	c.974+23561A>G		intron	N/A	NP_001129575.2
	TMEM132C	NM_001387058.1		c.914+23561A>G		intron	N/A	NP_001373987.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM132C	ENST00000435159.3	TSL:5 MANE Select	c.974+23561A>G		intron	N/A	ENSP00000410852.2
	ENSG00000256630	ENST00000535243.1	TSL:6	n.26T>C		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.402 AC: 74 AN: 184

American (AMR) AF: 0.276 AC: 475 AN: 1724

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 87 AN: 174

East Asian (EAS) AF: 0.597 AC: 393 AN: 658

South Asian (SAS) AF: 0.456 AC: 261 AN: 572

European-Finnish (FIN) AF: 0.529 AC: 598 AN: 1130

Middle Eastern (MID) AF: 0.307 AC: 27 AN: 88

European-Non Finnish (NFE) AF: 0.436 AC: 3325 AN: 7632

Other (OTH) AF: 0.445 AC: 259 AN: 582

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

African (AFR) AF: 0.268 AC: 11120 AN: 41446

American (AMR) AF: 0.231 AC: 3533 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1196 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2204 AN: 5146

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4814

European-Finnish (FIN) AF: 0.452 AC: 4774 AN: 10560

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22553 AN: 67956

Other (OTH) AF: 0.300 AC: 634 AN: 2112

Alfa AF: 0.314 Hom.: 14155

Bravo AF: 0.296

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.99
DANN	Benign	0.46
PhyloP100		1.6
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: rs10773543; hg19: chr12-128923726;