Genetic Variant TMPRSS5:c.1206+47T>G (chr11-113690184-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_030770.4(TMPRSS5):c.1206+47T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 0 hom., cov: 0)

Exomes 𝑓: 0.17 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMPRSS5
NM_030770.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.553

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-113690184-A-C is Benign according to our data. Variant chr11-113690184-A-C is described in ClinVar as [Benign]. Clinvar id is 1276785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS5	NM_030770.4 link	c.1206+47T>G		intron_variant	Intron 11 of 12	ENST00000299882.11	NP_110397.2	Q9H3S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11 link	c.1206+47T>G		intron_variant	Intron 11 of 12	1	NM_030770.4	ENSP00000299882.5		Q9H3S3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

999

AN:

21678

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0468

Gnomad AMI

AF:

0.0806

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.0247

Gnomad SAS

AF:

0.0407

Gnomad FIN

AF:

0.0567

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0464

Gnomad OTH

AF:

0.0571

GnomAD3 exomes

AF:

0.388

AC:

10826

AN:

27904

Hom.:

AF XY:

0.407

AC XY:

6758

AN XY:

16618

show subpopulations

Gnomad AFR exome

AF:

0.0909

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.0803

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.168

AC:

25615

AN:

152164

Hom.:

Cov.:

AF XY:

0.173

AC XY:

14011

AN XY:

81060

show subpopulations

Gnomad4 AFR exome

AF:

0.0978

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.0617

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0462

AC:

1004

AN:

21712

Hom.:

Cov.:

AF XY:

0.0458

AC XY:

494

AN XY:

10792

show subpopulations

Gnomad4 AFR

AF:

0.0471

Gnomad4 AMR

AF:

0.0455

Gnomad4 ASJ

AF:

0.0279

Gnomad4 EAS

AF:

0.0263

Gnomad4 SAS

AF:

0.0405

Gnomad4 FIN

AF:

0.0567

Gnomad4 NFE

AF:

0.0464

Gnomad4 OTH

AF:

0.0563

Alfa

AF:

0.0136

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.83

CADD

Benign

1.7

DANN

Benign

0.76

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