rs747929698

Variant names:

• chr12-50843118-C-T
• rs747929698
• NM_182559.3:c.154C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-50843118-C-T
• chr12-50843118-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182559.3(TMPRSS12):​c.154C>T​(p.Arg52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,575,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: TMPRSS12 NM_182559.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.85
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058918476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS12	NM_182559.3	MANE Select	c.154C>T	p.Arg52Trp	missense	Exon 1 of 5	NP_872365.2	Q86WS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS12	ENST00000398458.4	TSL:1 MANE Select	c.154C>T	p.Arg52Trp	missense	Exon 1 of 5	ENSP00000381476.3	Q86WS5
	TMPRSS12	ENST00000551456.5	TSL:2	c.154C>T	p.Arg52Trp	missense	Exon 1 of 4	ENSP00000447259.1	F8WBX2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000216 AC: 4 AN: 185382 AF XY: 0.0000201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000726

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000384

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000148 AC: 21 AN: 1423442 Hom.: 0 Cov.: 32 AF XY: 0.00000994 AC XY: 7 AN XY: 704404

African (AFR) AF: 0.0000608 AC: 2 AN: 32874

American (AMR) AF: 0.00 AC: 0 AN: 38054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25428

East Asian (EAS) AF: 0.0000525 AC: 2 AN: 38100

South Asian (SAS) AF: 0.00 AC: 0 AN: 81276

European-Finnish (FIN) AF: 0.0000793 AC: 4 AN: 50442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.0000119 AC: 13 AN: 1092538

Other (OTH) AF: 0.00 AC: 0 AN: 59000

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152162 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000506 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	2.6
DANN	Benign	0.95
DEOGEN2	Benign	0.020	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.0	N
PhyloP100		-4.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.45	N
REVEL	Uncertain	0.29
Sift	Benign	0.046	D
Sift4G	Uncertain	0.032	D
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.48		Gain of loop (P = 0.0435)
MVP		0.21
MPC		0.15
ClinPred		0.040	T
GERP RS		-5.8
PromoterAI		-0.038	Neutral
Varity_R		0.031
gMVP		0.47
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747929698; hg19: chr12-51236901;