11-113690196-A-C

Variant names:

• chr11-113690196-A-C
• rs754202991
• NM_030770.4:c.1206+35T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_030770.4(TMPRSS5):​c.1206+35T>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 0.023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMPRSS5 NM_030770.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.174
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-113690196-A-C is Benign according to our data. Variant chr11-113690196-A-C is described in ClinVar as Benign. ClinVar VariationId is 682805.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1206+35T>G		intron	N/A	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.1179+35T>G		intron	N/A	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.1074+35T>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.1206+35T>G		intron	N/A	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.1179+35T>G		intron	N/A	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.1074+35T>G		intron	N/A	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 475 AN: 20830 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0377

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00706

Gnomad SAS AF: 0.00839

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0321

GnomAD2 exomes AF: 0.0702 AC: 1654 AN: 23564 AF XY: 0.0763

Gnomad AFR exome AF: 0.00826

Gnomad AMR exome AF: 0.0700

Gnomad ASJ exome AF: 0.0954

Gnomad EAS exome AF: 0.0140

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.0587

Gnomad OTH exome AF: 0.0907

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0215 AC: 4559 AN: 212386 Hom.: 0 Cov.: 3 AF XY: 0.0236 AC XY: 2623 AN XY: 111146

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0101 AC: 44 AN: 4372

American (AMR) AF: 0.0191 AC: 90 AN: 4700

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 73 AN: 6332

East Asian (EAS) AF: 0.0142 AC: 71 AN: 5014

South Asian (SAS) AF: 0.0399 AC: 902 AN: 22586

European-Finnish (FIN) AF: 0.0205 AC: 317 AN: 15478

Middle Eastern (MID) AF: 0.0184 AC: 13 AN: 708

European-Non Finnish (NFE) AF: 0.0198 AC: 2836 AN: 143572

Other (OTH) AF: 0.0221 AC: 213 AN: 9624

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0228 AC: 477 AN: 20876 Hom.: 0 Cov.: 0 AF XY: 0.0227 AC XY: 232 AN XY: 10224

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0244 AC: 134 AN: 5492

American (AMR) AF: 0.0260 AC: 52 AN: 1998

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 5 AN: 468

East Asian (EAS) AF: 0.00852 AC: 6 AN: 704

South Asian (SAS) AF: 0.00836 AC: 5 AN: 598

European-Finnish (FIN) AF: 0.0298 AC: 38 AN: 1276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 38

European-Non Finnish (NFE) AF: 0.0226 AC: 224 AN: 9910

Other (OTH) AF: 0.0315 AC: 9 AN: 286

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs754202991;

hg19: chr11-113560918;