dbSNP rs11214703: TMPRSS5:p.Cys378Cys (chr11-113690303-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030770.4(TMPRSS5):c.1134C>T(p.Cys378Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,593,688 control chromosomes in the GnomAD database, including 3,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 505 hom., cov: 28)

Exomes 𝑓: 0.026 ( 3258 hom. )

Consequence

TMPRSS5
NM_030770.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

TMPRSS5 (HGNC:14908): (transmembrane serine protease 5) This gene encodes a protein that belongs to the serine protease family. Serine proteases are known to be involved in many physiological and pathological processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TMPRSS5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 11-113690303-G-A is Benign according to our data. Variant chr11-113690303-G-A is described in ClinVar as [Benign]. Clinvar id is 508576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS5	NM_030770.4 link	c.1134C>T	p.Cys378Cys	synonymous_variant	Exon 11 of 13	ENST00000299882.11	NP_110397.2	Q9H3S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11 link	c.1134C>T	p.Cys378Cys	synonymous_variant	Exon 11 of 13	1	NM_030770.4	ENSP00000299882.5		Q9H3S3

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6555

AN:

151844

Hom.:

496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.00632

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.0498

GnomAD3 exomes

AF:

0.0733

AC:

15986

AN:

218182

Hom.:

2051

AF XY:

0.0640

AC XY:

7523

AN XY:

117620

show subpopulations

Gnomad AFR exome

AF:

0.0406

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.350

Gnomad SAS exome

AF:

0.0487

Gnomad FIN exome

AF:

0.00580

Gnomad NFE exome

AF:

0.00863

Gnomad OTH exome

AF:

0.0500

GnomAD4 exome

AF:

0.0262

AC:

37749

AN:

1441726

Hom.:

3258

Cov.:

AF XY:

0.0259

AC XY:

18517

AN XY:

714840

show subpopulations

Gnomad4 AFR exome

AF:

0.0390

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.0477

Gnomad4 FIN exome

AF:

0.00568

Gnomad4 NFE exome

AF:

0.00813

Gnomad4 OTH exome

AF:

0.0418

GnomAD4 genome

AF:

0.0434

AC:

6593

AN:

151962

Hom.:

505

Cov.:

AF XY:

0.0464

AC XY:

3448

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.0598

Gnomad4 FIN

AF:

0.00632

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.0559

Alfa

AF:

0.0204

Hom.:

206

Bravo

AF:

0.0568

Asia WGS

AF:

0.187

AC:

650

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 13, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.9

DANN

Benign

0.67

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