12-125377595-T-C

Position:

• chr12-125377595-T-C

Variant summary

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

The NM_001366854.1(TMEM132B):​c.959+27252T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,026 control chromosomes in the GnomAD database, including 3,664 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 0.21 (3664 hom., cov: 32)
• Consequence: TMEM132B NM_001366854.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

Genes affected

TMEM132B (HGNC:29397): (transmembrane protein 132B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM132B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM132B	NM_001366854.1	c.959+27252T>C		intron_variant		ENST00000682704.1	NP_001353783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM132B	ENST00000682704.1	c.959+27252T>C		intron_variant			NM_001366854.1	ENSP00000507790.1
TMEM132B	ENST00000299308.7	c.944+27252T>C		intron_variant		5		ENSP00000299308.3
TMEM132B	ENST00000534945.2	n.892+27252T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31561 AN: 151908 Hom.: 3658 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.208 AC: 31596 AN: 152026 Hom.: 3664 Cov.: 32 AF XY: 0.213 AC XY: 15846 AN XY: 74304

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.191

Alfa AF: 0.158 Hom.: 2712

Bravo AF: 0.205

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.52

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: rs3847938; hg19: chr12-125862141;