rs767641919

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-113690184-A-C
• chr11-113690184-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -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 VariationId is 1276785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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+47T>G		intron	N/A	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.1179+47T>G		intron	N/A	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.1074+47T>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+47T>G		intron	N/A	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.1179+47T>G		intron	N/A	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.1074+47T>G		intron	N/A	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 999 AN: 21678 Hom.: 0 Cov.: 0

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

GnomAD2 exomes AF: 0.388 AC: 10826 AN: 27904 AF XY: 0.407

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 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.: 0 Cov.: 3 AF XY: 0.173 AC XY: 14011 AN XY: 81060

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

African (AFR) AF: 0.0978 AC: 296 AN: 3026

American (AMR) AF: 0.136 AC: 494 AN: 3622

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 656 AN: 4414

East Asian (EAS) AF: 0.0617 AC: 328 AN: 5316

South Asian (SAS) AF: 0.200 AC: 3601 AN: 18032

European-Finnish (FIN) AF: 0.137 AC: 1257 AN: 9142

Middle Eastern (MID) AF: 0.118 AC: 72 AN: 608

European-Non Finnish (NFE) AF: 0.178 AC: 17848 AN: 100176

Other (OTH) AF: 0.136 AC: 1063 AN: 7828

⚠️ 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: 0.0462 AC: 1004 AN: 21712 Hom.: 0 Cov.: 0 AF XY: 0.0458 AC XY: 494 AN XY: 10792

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

African (AFR) AF: 0.0471 AC: 279 AN: 5922

American (AMR) AF: 0.0455 AC: 116 AN: 2548

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 13 AN: 466

East Asian (EAS) AF: 0.0263 AC: 16 AN: 608

South Asian (SAS) AF: 0.0405 AC: 25 AN: 618

European-Finnish (FIN) AF: 0.0567 AC: 85 AN: 1498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 28

European-Non Finnish (NFE) AF: 0.0464 AC: 449 AN: 9678

Other (OTH) AF: 0.0563 AC: 16 AN: 284

⚠️ 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.

Alfa AF: 0.0136 Hom.: 0

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	-0.83
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.55
Mutation Taster		=3/97	disease causing

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: rs767641919;

hg19: chr11-113560906;