3-112042006-G-A

Position:

• chr3-112042006-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395507.1(TMPRSS7):​c.385G>A​(p.Glu129Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TMPRSS7 NM_001395507.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.67

Genes affected

TMPRSS7 (HGNC:30846): (transmembrane serine protease 7) Predicted to enable serine-type peptidase activity. Predicted to be involved in proteolysis. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMPRSS7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33241463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1	c.385G>A	p.Glu129Lys	missense_variant	3/18	ENST00000452346.7	NP_001382436.1
TMPRSS7	NM_001042575.2	c.49G>A	p.Glu17Lys	missense_variant	2/16		NP_001036040.2
TMPRSS7	XM_011512754.2	c.136G>A	p.Glu46Lys	missense_variant	2/17		XP_011511056.1
TMPRSS7	NR_026734.1	n.219G>A		non_coding_transcript_exon_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS7	ENST00000452346.7	c.385G>A	p.Glu129Lys	missense_variant	3/18	5	NM_001395507.1	ENSP00000398236.2
TMPRSS7	ENST00000419127.5	c.49G>A	p.Glu17Lys	missense_variant	2/16	1		ENSP00000411645.1
TMPRSS7	ENST00000617607.4	c.49G>A	p.Glu17Lys	missense_variant	1/15	5		ENSP00000478830.1
TMPRSS7	ENST00000435737.5	n.49G>A		non_coding_transcript_exon_variant	2/17	2		ENSP00000415472.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.49G>A (p.E17K) alteration is located in exon 2 (coding exon 1) of the TMPRSS7 gene. This alteration results from a G to A substitution at nucleotide position 49, causing the glutamic acid (E) at amino acid position 17 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N;N;.
REVEL	Benign	0.26
Sift	Benign	0.095	T;T;.
Sift4G	Benign	0.10	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.45
MutPred		0.41		.;Gain of MoRF binding (P = 0.0117);Gain of MoRF binding (P = 0.0117);
MVP		0.27
MPC		0.35
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-111760853;