Variant 4-68064889-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207407.2(TMPRSS11F):c.811G>A(p.Ala271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

TMPRSS11F
NM_207407.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

Variant links:

Genes affected

TMPRSS11F (HGNC:29994): (transmembrane serine protease 11F) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within regulation of water loss via skin. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

TMPRSS11F links:

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

UBA6-DT links:

LOC550113 (HGNC:):

LOC550113 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07494855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11F	NM_207407.2 linkuse as main transcript	c.811G>A	p.Ala271Thr	missense_variant	8/10	ENST00000356291.3	NP_997290.2
LOC550113	NR_046116.1 linkuse as main transcript	n.2658+1668C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11F	ENST00000356291.3 linkuse as main transcript	c.811G>A	p.Ala271Thr	missense_variant	8/10	2	NM_207407.2	ENSP00000348639	P1
UBA6-DT	ENST00000500538.7 linkuse as main transcript	n.2602+1668C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

251022

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 16, 2021

The c.811G>A (p.A271T) alteration is located in exon 8 (coding exon 8) of the TMPRSS11F gene. This alteration results from a G to A substitution at nucleotide position 811, causing the alanine (A) at amino acid position 271 to be replaced by a threonine (T). 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

0.071

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.9

DANN

Benign

0.97

DEOGEN2

Benign

0.057

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.47

M_CAP

Benign

0.065

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.58

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.77

REVEL

Benign

0.22

Sift

Benign

0.18

Sift4G

Benign

0.59

Polyphen

0.87

Vest4

0.12

MutPred

0.33

Gain of phosphorylation at A271 (P = 0.0177);

MVP

0.63

MPC

0.066

ClinPred

0.025

GERP RS

2.7

Varity_R

0.037

gMVP

0.45

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