Variant 3-112061801-A-T 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.1325A>T(p.Tyr442Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,456,954 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TMPRSS7
NM_001395507.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

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:

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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/exons	MANE	UniProt
TMPRSS7	NM_001395507.1 linkuse as main transcript	c.1325A>T	p.Tyr442Phe	missense_variant	11/18	ENST00000452346.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS7	ENST00000452346.7 linkuse as main transcript	c.1325A>T	p.Tyr442Phe	missense_variant	11/18	5	NM_001395507.1		Q7RTY8-1
TMPRSS7	ENST00000419127.5 linkuse as main transcript	c.947A>T	p.Tyr316Phe	missense_variant	9/16	1		P1	Q7RTY8-2
TMPRSS7	ENST00000617607.4 linkuse as main transcript	c.947A>T	p.Tyr316Phe	missense_variant	8/15	5		P1	Q7RTY8-2
TMPRSS7	ENST00000435737.5 linkuse as main transcript	c.*670A>T		3_prime_UTR_variant, NMD_transcript_variant	10/17	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246166

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1456954

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724682

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000541

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

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

Apr 10, 2023

The c.947A>T (p.Y316F) alteration is located in exon 9 (coding exon 8) of the TMPRSS7 gene. This alteration results from a A to T substitution at nucleotide position 947, causing the tyrosine (Y) at amino acid position 316 to be replaced by a phenylalanine (F). 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

0.099

BayesDel_addAF

Benign

-0.0066

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.0087

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.19

Sift

Benign

0.032

D;D;.

Sift4G

Benign

0.40

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.68

MutPred

0.43

Gain of glycosylation at Y442 (P = 0.0308);.;.;

MVP

0.61

MPC

0.40

ClinPred

0.80

GERP RS

5.6

Varity_R

0.19

gMVP

0.25

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