Variant chr4-68471483-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014058.4(TMPRSS11E):c.350C>T(p.Ala117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 1,559,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TMPRSS11E
NM_014058.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

TMPRSS11E (HGNC:24465): (transmembrane serine protease 11E) Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMPRSS11E 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=0.34573108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMPRSS11E	NM_014058.4 linkuse as main transcript	c.350C>T	p.Ala117Val	missense_variant	5/10	ENST00000305363.9
TMPRSS11E	XM_011531896.3 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	4/9
TMPRSS11E	XM_047450139.1 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS11E	ENST00000305363.9 linkuse as main transcript	c.350C>T	p.Ala117Val	missense_variant	5/10	1	NM_014058.4	P1
TMPRSS11E	ENST00000510647.1 linkuse as main transcript	c.315+2537C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000354

AC:

AN:

1411792

Hom.:

Cov.:

AF XY:

0.00000570

AC XY:

AN XY:

702188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000503

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:

0.00000277

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147744

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71768

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jan 03, 2022

The c.350C>T (p.A117V) alteration is located in exon 5 (coding exon 5) of the TMPRSS11E gene. This alteration results from a C to T substitution at nucleotide position 350, causing the alanine (A) at amino acid position 117 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.020

Eigen

Benign

0.032

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Benign

0.020

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.74

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.90

REVEL

Benign

0.29

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

1.0

Vest4

0.42

MutPred

0.58

Gain of sheet (P = 0.0344);

MVP

0.50

MPC

0.48

ClinPred

0.68

GERP RS

5.1

Varity_R

0.10

gMVP

0.42

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