Variant 4-68053970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_207407.2(TMPRSS11F):c.1256C>T(p.Pro419Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMPRSS11F
NM_207407.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11F	NM_207407.2 link	c.1256C>T	p.Pro419Leu	missense_variant	10/10	ENST00000356291.3	NP_997290.2	Q6ZWK6
TMPRSS11F	XM_047415669.1 link	c.725C>T	p.Pro242Leu	missense_variant	7/7		XP_047271625.1
TMPRSS11F	XM_047415670.1 link	c.725C>T	p.Pro242Leu	missense_variant	9/9		XP_047271626.1
LOC550113	NR_046116.1 link	n.51+412G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMPRSS11F	ENST00000356291.3 link	c.1256C>T	p.Pro419Leu	missense_variant	10/10	2	NM_207407.2	ENSP00000348639.2	Q6ZWK6
UBA6-DT	ENST00000500538.7 link	n.1988-8637G>A		intron_variant		1
UBA6-DT	ENST00000663060.1 link	n.1554-26151G>A		intron_variant
UBA6-DT	ENST00000667140.1 link	n.1811-23309G>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249706

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461460

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 01, 2024

The c.1256C>T (p.P419L) alteration is located in exon 10 (coding exon 10) of the TMPRSS11F gene. This alteration results from a C to T substitution at nucleotide position 1256, causing the proline (P) at amino acid position 419 to be replaced by a leucine (L). 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

0.80

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.47

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.97

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-9.5

REVEL

Pathogenic

0.96

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MutPred

0.86

Gain of MoRF binding (P = 0.0461);

MVP

0.97

MPC

0.40

ClinPred

1.0

GERP RS

5.8

Varity_R

0.84

gMVP

0.95

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