12-50879648-A-G

Position:

• chr12-50879648-A-G

Variant summary

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

The NM_182559.3(TMPRSS12):​c.653-5598A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,082 control chromosomes in the GnomAD database, including 23,817 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 0.56 (23817 hom., cov: 32)
• Consequence: TMPRSS12 NM_182559.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

Genes affected

TMPRSS12 (HGNC:28779): (transmembrane serine protease 12) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within binding activity of sperm to zona pellucida and protein processing. Predicted to be located in acrosomal vesicle. 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS12	NM_182559.3	c.653-5598A>G		intron_variant		ENST00000398458.4	NP_872365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS12	ENST00000398458.4	c.653-5598A>G		intron_variant		1	NM_182559.3	ENSP00000381476	P1
TMPRSS12	ENST00000551456.5	c.653-5598A>G		intron_variant		2		ENSP00000447259

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84750 AN: 151964 Hom.: 23780 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.558 AC: 84838 AN: 152082 Hom.: 23817 Cov.: 32 AF XY: 0.560 AC XY: 41665 AN XY: 74356

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.542

Alfa AF: 0.561 Hom.: 48277

Bravo AF: 0.552

Asia WGS AF: 0.616 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.47

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: rs4768933; hg19: chr12-51273431;