3-112042006-G-A

Variant names:

• chr3-112042006-G-A
• NM_001395507.1:c.385G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395507.1. 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
	TMPRSS7	NM_001395507.1	MANE Select	c.385G>A	p.Glu129Lys	missense	Exon 3 of 18	NP_001382436.1	Q7RTY8-1
	TMPRSS7	NM_001042575.2		c.49G>A	p.Glu17Lys	missense	Exon 2 of 16	NP_001036040.2	Q7RTY8-2
	TMPRSS7	NR_026734.1		n.219G>A		non_coding_transcript_exon	Exon 2 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS7	ENST00000452346.7	TSL:5 MANE Select	c.385G>A	p.Glu129Lys	missense	Exon 3 of 18	ENSP00000398236.2	Q7RTY8-1
	TMPRSS7	ENST00000419127.5	TSL:1	c.49G>A	p.Glu17Lys	missense	Exon 2 of 16	ENSP00000411645.1	Q7RTY8-2
	TMPRSS7	ENST00000617607.4	TSL:5	c.49G>A	p.Glu17Lys	missense	Exon 1 of 15	ENSP00000478830.1	Q7RTY8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.17
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
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.26
Sift	Benign	0.095	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.41		Gain of MoRF binding (P = 0.0117)
MVP		0.27
MPC		0.35
ClinPred		0.96	D
GERP RS		4.7
PromoterAI		-0.00090	Neutral
Varity_R		0.12
gMVP		0.35
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

hg19: chr3-111760853;