11-113690525-T-C

Variant names:

• chr11-113690525-T-C
• rs11601435
• NM_030770.4:c.1064-152A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030770.4(TMPRSS5):​c.1064-152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,678 control chromosomes in the GnomAD database, including 2,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.17 (2179 hom., cov: 30)
• Consequence: TMPRSS5 NM_030770.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.301
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-113690525-T-C is Benign according to our data. Variant chr11-113690525-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS5	NM_030770.4	MANE Select	c.1064-152A>G		intron	N/A	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.1037-152A>G		intron	N/A	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.932-152A>G		intron	N/A	NP_001275679.1	F5H2M3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS5	ENST00000299882.11	TSL:1 MANE Select	c.1064-152A>G		intron	N/A	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.1037-152A>G		intron	N/A	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.932-152A>G		intron	N/A	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25330 AN: 151560 Hom.: 2176 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25346 AN: 151678 Hom.: 2179 Cov.: 30 AF XY: 0.166 AC XY: 12306 AN XY: 74088

African (AFR) AF: 0.166 AC: 6882 AN: 41340

American (AMR) AF: 0.130 AC: 1988 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 746 AN: 3456

East Asian (EAS) AF: 0.0882 AC: 453 AN: 5134

South Asian (SAS) AF: 0.188 AC: 903 AN: 4802

European-Finnish (FIN) AF: 0.153 AC: 1614 AN: 10532

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12180 AN: 67848

Other (OTH) AF: 0.180 AC: 377 AN: 2100

Alfa AF: 0.177 Hom.: 1059

Bravo AF: 0.164

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11601435; hg19: chr11-113561247;