Variant 3-112049960-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395507.1(TMPRSS7):c.1076T>C(p.Val359Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000777 in 1,569,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V359F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

TMPRSS7
NM_001395507.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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 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=0.017654628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS7	NM_001395507.1 linkuse as main transcript	c.1076T>C	p.Val359Ala	missense_variant	8/18	ENST00000452346.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS7	ENST00000452346.7 linkuse as main transcript	c.1076T>C	p.Val359Ala	missense_variant	8/18	5	NM_001395507.1		Q7RTY8-1
TMPRSS7	ENST00000419127.5 linkuse as main transcript	c.698T>C	p.Val233Ala	missense_variant	6/16	1		P1	Q7RTY8-2
TMPRSS7	ENST00000617607.4 linkuse as main transcript	c.698T>C	p.Val233Ala	missense_variant	5/15	5		P1	Q7RTY8-2
TMPRSS7	ENST00000435737.5 linkuse as main transcript	c.*421T>C		3_prime_UTR_variant, NMD_transcript_variant	7/17	2

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000948

AC:

AN:

242490

Hom.:

AF XY:

0.0000684

AC XY:

AN XY:

131498

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.0000307

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:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000494

AC:

AN:

1417300

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

699578

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.0000692

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:

0.00000555

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.000341

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000178

Hom.:

Bravo

AF:

0.000370

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.698T>C (p.V233A) alteration is located in exon 6 (coding exon 5) of the TMPRSS7 gene. This alteration results from a T to C substitution at nucleotide position 698, causing the valine (V) at amino acid position 233 to be replaced by an alanine (A). 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

0.23

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.0050

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.58

T;.;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

MutationTaster

Benign

0.91

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.44

N;N;.

REVEL

Benign

0.044

Sift

Benign

0.83

T;T;.

Sift4G

Benign

0.87

T;T;T

Polyphen

0.057

B;B;B

Vest4

0.31

MVP

0.095

MPC

0.089

ClinPred

0.039

GERP RS

4.0

Varity_R

0.051

gMVP

0.46

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

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