11-113688168-G-A

Variant names:

• chr11-113688168-G-A
• rs116205432
• NM_030770.4:c.*92C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030770.4(TMPRSS5):​c.*92C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,509,722 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (20 hom.)
• Consequence: TMPRSS5 NM_030770.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.126
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-113688168-G-A is Benign according to our data. Variant chr11-113688168-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1318211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00924 (1407/152296) while in subpopulation AFR AF = 0.0317 (1316/41566). AF 95% confidence interval is 0.0302. There are 19 homozygotes in GnomAd4. There are 654 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1407 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS5	NM_030770.4	MANE Select	c.*92C>T		3_prime_UTR	Exon 13 of 13	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.*92C>T		3_prime_UTR	Exon 13 of 13	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.*92C>T		3_prime_UTR	Exon 12 of 12	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.*92C>T		3_prime_UTR	Exon 13 of 13	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.*92C>T		3_prime_UTR	Exon 13 of 13	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.*92C>T		3_prime_UTR	Exon 12 of 12	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes AF: 0.00925 AC: 1407 AN: 152178 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.000953 AC: 1294 AN: 1357426 Hom.: 20 Cov.: 30 AF XY: 0.000860 AC XY: 573 AN XY: 666344

African (AFR) AF: 0.0358 AC: 1079 AN: 30120

American (AMR) AF: 0.00239 AC: 70 AN: 29260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22330

East Asian (EAS) AF: 0.00 AC: 0 AN: 35084

South Asian (SAS) AF: 0.000114 AC: 8 AN: 70344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47588

Middle Eastern (MID) AF: 0.000965 AC: 5 AN: 5182

European-Non Finnish (NFE) AF: 0.0000198 AC: 21 AN: 1061204

Other (OTH) AF: 0.00197 AC: 111 AN: 56314

GnomAD4 genome AF: 0.00924 AC: 1407 AN: 152296 Hom.: 19 Cov.: 32 AF XY: 0.00878 AC XY: 654 AN XY: 74460

African (AFR) AF: 0.0317 AC: 1316 AN: 41566

American (AMR) AF: 0.00431 AC: 66 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00530 Hom.: 8

Bravo AF: 0.0109

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.85
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		0.13
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs116205432; hg19: chr11-113558890;