4-67838318-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004262.3(TMPRSS11D):c.329G>A(p.Ser110Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,568,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

TMPRSS11D
NM_004262.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.03

Publications

5 publications found

Variant links:

Genes affected

TMPRSS11D (HGNC:24059): (transmembrane serine protease 11D) This gene encodes a trypsin-like serine protease released from the submucosal serous glands onto mucous membrane. It is a type II integral membrane protein and has 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region has little similarity to other known proteins. This protein may play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]

TMPRSS11D links:

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

UBA6-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0114963055).

BP6

Variant 4-67838318-C-T is Benign according to our data. Variant chr4-67838318-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2232113.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004262.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11D	NM_004262.3	MANE Select	c.329G>A	p.Ser110Asn	missense	Exon 5 of 10	NP_004253.1	O60235

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMPRSS11D	ENST00000283916.11	TSL:1 MANE Select	c.329G>A	p.Ser110Asn	missense	Exon 5 of 10	ENSP00000283916.6	O60235
UBA6-DT	ENST00000500538.7	TSL:1	n.1987+83063C>T		intron	N/A
TMPRSS11D	ENST00000502573.5	TSL:4	n.187G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000521

AC:

111

AN:

213064

AF XY:

0.000501

show subpopulations

Gnomad AFR exome

AF:

0.000274

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000541

AC:

766

AN:

1416030

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

370

AN XY:

702766

show subpopulations

African (AFR)

AF:

0.000129

AC:

AN:

31100

American (AMR)

AF:

0.00107

AC:

AN:

34430

Ashkenazi Jewish (ASJ)

AF:

0.00151

AC:

AN:

24474

East Asian (EAS)

AF:

0.00

AC:

AN:

38020

South Asian (SAS)

AF:

0.000116

AC:

AN:

77408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52598

Middle Eastern (MID)

AF:

0.000537

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.000583

AC:

638

AN:

1093950

Other (OTH)

AF:

0.000650

AC:

AN:

58460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.000552

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41544

American (AMR)

AF:

0.00190

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

67974

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000543

Hom.:

Bravo

AF:

0.000533

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000371

AC:

ClinVar

ClinVar submissions

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

0.066

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0040

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.14

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.45

M_CAP

Benign

0.0043

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.010

PhyloP100

-4.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.54

REVEL

Benign

0.070

Sift

Benign

0.54

Sift4G

Benign

0.94

Polyphen

0.0020

Vest4

0.099

MVP

0.21

MPC

0.082

ClinPred

0.0025

GERP RS

-6.3

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.035

gMVP

0.12

Mutation Taster

=99/1

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