Variant 3-112057107-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001395507.1(TMPRSS7):c.1286G>A(p.Gly429Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,612,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

TMPRSS7
NM_001395507.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.62

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.290524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS7	NM_001395507.1 linkuse as main transcript	c.1286G>A	p.Gly429Glu	missense_variant	10/18	ENST00000452346.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS7	ENST00000452346.7 linkuse as main transcript	c.1286G>A	p.Gly429Glu	missense_variant	10/18	5	NM_001395507.1		Q7RTY8-1
TMPRSS7	ENST00000419127.5 linkuse as main transcript	c.908G>A	p.Gly303Glu	missense_variant	8/16	1		P1	Q7RTY8-2
TMPRSS7	ENST00000617607.4 linkuse as main transcript	c.908G>A	p.Gly303Glu	missense_variant	7/15	5		P1	Q7RTY8-2
TMPRSS7	ENST00000435737.5 linkuse as main transcript	c.*631G>A		3_prime_UTR_variant, NMD_transcript_variant	9/17	2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000844

AC:

AN:

248726

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134952

show subpopulations

Gnomad AFR exome

AF:

0.000971

Gnomad AMR exome

AF:

0.000146

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1459998

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000230

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.0000654

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:

0.000473

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.000785

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000745

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

May 25, 2022

The c.908G>A (p.G303E) alteration is located in exon 8 (coding exon 7) of the TMPRSS7 gene. This alteration results from a G to A substitution at nucleotide position 908, causing the glycine (G) at amino acid position 303 to be replaced by a glutamic acid (E). 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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Uncertain

0.040

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

D;.;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.2

N;N;.

REVEL

Uncertain

0.48

Sift

Uncertain

0.028

D;T;.

Sift4G

Benign

0.39

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.91

MVP

0.32

MPC

0.47

ClinPred

0.13

GERP RS

5.9

Varity_R

0.48

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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