Genetic Variant TMPRSS5:c.1206+35T>C (chr11-113690196-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_030770.4(TMPRSS5):c.1206+35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0041 ( 1 hom. )

Consequence

TMPRSS5
NM_030770.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.174

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

TMPRSS5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS2

High AC in GnomAd4 at 56 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030770.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMPRSS5	NM_030770.4	MANE Select	c.1206+35T>C	intron	N/A	NP_110397.2	Q9H3S3
TMPRSS5	NM_001288751.2		c.1179+35T>C	intron	N/A	NP_001275680.1	F5GX83
TMPRSS5	NM_001288750.2		c.1074+35T>C	intron	N/A	NP_001275679.1	F5H2M3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMPRSS5	ENST00000299882.11	TSL:1 MANE Select	c.1206+35T>C	intron	N/A	ENSP00000299882.5	Q9H3S3
TMPRSS5	ENST00000545579.6	TSL:1	c.1179+35T>C	intron	N/A	ENSP00000441104.1	F5GX83
TMPRSS5	ENST00000538955.5	TSL:1	c.1074+35T>C	intron	N/A	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

AN:

22518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000681

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00305

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00450

Gnomad OTH

AF:

0.00671

GnomAD2 exomes

AF:

0.00199

AC:

AN:

23564

AF XY:

0.00251

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00345

Gnomad OTH exome

AF:

0.00403

GnomAD4 exome

AF:

0.00414

AC:

966

AN:

233060

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

494

AN XY:

122382

show subpopulations

African (AFR)

AF:

0.000424

AC:

AN:

4714

American (AMR)

AF:

0.000964

AC:

AN:

5188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6900

East Asian (EAS)

AF:

0.00

AC:

AN:

5448

South Asian (SAS)

AF:

0.00157

AC:

AN:

25438

European-Finnish (FIN)

AF:

0.000120

AC:

AN:

16654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

774

European-Non Finnish (NFE)

AF:

0.00547

AC:

861

AN:

157348

Other (OTH)

AF:

0.00529

AC:

AN:

10596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.00249

AC:

AN:

22518

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

AN XY:

11072

show subpopulations

African (AFR)

AF:

0.000681

AC:

AN:

5876

American (AMR)

AF:

0.00

AC:

AN:

2206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

512

East Asian (EAS)

AF:

0.00

AC:

AN:

732

South Asian (SAS)

AF:

0.00305

AC:

AN:

656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00450

AC:

AN:

10662

Other (OTH)

AF:

0.00671

AC:

AN:

298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

(source)

DANN

Benign

0.73

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

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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