11-118111842-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_019894.4(TMPRSS4):c.685G>A(p.Val229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,608,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TMPRSS4
NM_019894.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.140

Publications

0 publications found

Variant links:

Genes affected

TMPRSS4 (HGNC:11878): (transmembrane serine protease 4) This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

TMPRSS4 Gene-Disease associations (from GenCC):

autosomal recessive cerebral atrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMPRSS4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10289389).

BP6

Variant 11-118111842-G-A is Benign according to our data. Variant chr11-118111842-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2514518.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019894.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS4	NM_019894.4	MANE Select	c.685G>A	p.Val229Ile	missense	Exon 8 of 13	NP_063947.2	Q9NRS4-1
TMPRSS4	NM_001173551.2		c.679G>A	p.Val227Ile	missense	Exon 8 of 13	NP_001167022.2	Q9NRS4-3
TMPRSS4	NM_001083947.2		c.670G>A	p.Val224Ile	missense	Exon 8 of 13	NP_001077416.2	Q9NRS4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS4	ENST00000437212.8	TSL:1 MANE Select	c.685G>A	p.Val229Ile	missense	Exon 8 of 13	ENSP00000416037.3	Q9NRS4-1
TMPRSS4	ENST00000522824.5	TSL:1	c.670G>A	p.Val224Ile	missense	Exon 8 of 13	ENSP00000430547.1	Q9NRS4-2
TMPRSS4	ENST00000714375.1		n.685G>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000519642.1	A0AAQ5BHV3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152212

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000489

AC:

AN:

245470

AF XY:

0.0000377

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1456388

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33158

American (AMR)

AF:

0.000228

AC:

AN:

43834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39120

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1109810

Other (OTH)

AF:

0.0000166

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000762

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.029

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.051

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.25

M_CAP

Benign

0.030

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.77

PhyloP100

-0.14

PrimateAI

Benign

0.26

PROVEAN

Benign

0.090

REVEL

Benign

0.25

Sift

Benign

1.0

Sift4G

Benign

0.97

Polyphen

0.0060

Vest4

0.022

MVP

0.42

MPC

0.098

ClinPred

0.016

GERP RS

-8.0

Varity_R

0.042

gMVP

0.15

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over