11-113690184-A-G

Variant names:

• chr11-113690184-A-G
• rs767641919
• NM_030770.4:c.1206+47T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030770.4(TMPRSS5):​c.1206+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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: not found (cov: 0)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: TMPRSS5 NM_030770.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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+47T>C		intron	N/A	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.1179+47T>C		intron	N/A	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.1074+47T>C		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+47T>C		intron	N/A	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.1179+47T>C		intron	N/A	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.1074+47T>C		intron	N/A	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000478 AC: 9 AN: 188320 Hom.: 0 Cov.: 3 AF XY: 0.0000495 AC XY: 5 AN XY: 101088

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

African (AFR) AF: 0.00 AC: 0 AN: 3558

American (AMR) AF: 0.00 AC: 0 AN: 4554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5714

East Asian (EAS) AF: 0.00 AC: 0 AN: 6376

South Asian (SAS) AF: 0.00 AC: 0 AN: 23560

European-Finnish (FIN) AF: 0.0000871 AC: 1 AN: 11480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 752

European-Non Finnish (NFE) AF: 0.0000652 AC: 8 AN: 122700

Other (OTH) AF: 0.00 AC: 0 AN: 9626

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.55

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: rs767641919; hg19: chr11-113560906;