Variant 3-112042015-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395507.1(TMPRSS7):c.394G>A(p.Glu132Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,551,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

TMPRSS7
NM_001395507.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.44

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS7	NM_001395507.1 link	c.394G>A	p.Glu132Lys	missense_variant	Exon 3 of 18	ENST00000452346.7	NP_001382436.1
TMPRSS7	NM_001042575.2 link	c.58G>A	p.Glu20Lys	missense_variant	Exon 2 of 16		NP_001036040.2	Q7RTY8-2
TMPRSS7	XM_011512754.2 link	c.145G>A	p.Glu49Lys	missense_variant	Exon 2 of 17		XP_011511056.1
TMPRSS7	NR_026734.1 link	n.228G>A		non_coding_transcript_exon_variant	Exon 2 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMPRSS7	ENST00000452346.7 link	c.394G>A	p.Glu132Lys	missense_variant	Exon 3 of 18	5	NM_001395507.1	ENSP00000398236.2	Q7RTY8-1
TMPRSS7	ENST00000419127.5 link	c.58G>A	p.Glu20Lys	missense_variant	Exon 2 of 16	1		ENSP00000411645.1	Q7RTY8-2
TMPRSS7	ENST00000617607.4 link	c.58G>A	p.Glu20Lys	missense_variant	Exon 1 of 15	5		ENSP00000478830.1	Q7RTY8-2
TMPRSS7	ENST00000435737.5 link	n.58G>A		non_coding_transcript_exon_variant	Exon 2 of 17	2		ENSP00000415472.1	F8WCZ2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

156534

Hom.:

AF XY:

0.0000844

AC XY:

AN XY:

82954

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000173

AC:

242

AN:

1399342

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

122

AN XY:

690182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.0000394

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58G>A (p.E20K) 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 58, causing the glutamic acid (E) at amino acid position 20 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

Uncertain

0.56

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.030

T;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;.;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.0

M;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.3

N;N;.

REVEL

Uncertain

0.42

Sift

Uncertain

0.0030

D;D;.

Sift4G

Benign

0.091

T;D;D

Polyphen

1.0

.;D;D

Vest4

0.76

MVP

0.65

MPC

0.41

ClinPred

0.21

GERP RS

5.5

Varity_R

0.40

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over