rs530967806

Variant names:

• chr12-50843092-A-G
• NM_182559.3:c.128A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-50843092-A-G
• chr12-50843092-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182559.3(TMPRSS12):​c.128A>G​(p.Gln43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q43L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPRSS12 NM_182559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05367425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS12	NM_182559.3	c.128A>G	p.Gln43Arg	missense_variant	Exon 1 of 5	ENST00000398458.4	NP_872365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS12	ENST00000398458.4	c.128A>G	p.Gln43Arg	missense_variant	Exon 1 of 5	1	NM_182559.3	ENSP00000381476.3
TMPRSS12	ENST00000551456.5	c.128A>G	p.Gln43Arg	missense_variant	Exon 1 of 4	2		ENSP00000447259.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.9
DANN	Benign	0.73
DEOGEN2	Benign	0.0030	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.10
Sift	Benign	0.48	T;T
Sift4G	Benign	0.83	T;T
Polyphen		0.0	B;B
Vest4		0.033
MutPred		0.27		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.51
MPC		0.16
ClinPred		0.046	T
GERP RS		-1.2
Varity_R		0.024
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-51236875;