rs79480579

Variant names:

• chr11-113690279-G-A
• rs79480579
• NM_030770.4:c.1158C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030770.4(TMPRSS5):​c.1158C>T​(p.Pro386Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,571,296 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (13 hom., cov: 28)
  • Exomes 𝑓: 0.00083 (12 hom.)
• Consequence: TMPRSS5 NM_030770.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.220
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-113690279-G-A is Benign according to our data. Variant chr11-113690279-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 508635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.22 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00562 (854/151996) while in subpopulation AFR AF = 0.0183 (758/41454). AF 95% confidence interval is 0.0172. There are 13 homozygotes in GnomAd4. There are 379 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High AC in GnomAd4 at 854 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.1158C>T	p.Pro386Pro	synonymous	Exon 11 of 13	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.1131C>T	p.Pro377Pro	synonymous	Exon 11 of 13	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.1026C>T	p.Pro342Pro	synonymous	Exon 10 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.1158C>T	p.Pro386Pro	synonymous	Exon 11 of 13	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.1131C>T	p.Pro377Pro	synonymous	Exon 11 of 13	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.1026C>T	p.Pro342Pro	synonymous	Exon 10 of 12	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes AF: 0.00562 AC: 854 AN: 151878 Hom.: 13 Cov.: 28

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00139 AC: 257 AN: 184878 AF XY: 0.00115

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000389

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000827 AC: 1174 AN: 1419300 Hom.: 12 Cov.: 52 AF XY: 0.000737 AC XY: 517 AN XY: 701804

African (AFR) AF: 0.0187 AC: 604 AN: 32244

American (AMR) AF: 0.00151 AC: 57 AN: 37708

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25252

East Asian (EAS) AF: 0.00 AC: 0 AN: 37010

South Asian (SAS) AF: 0.0000375 AC: 3 AN: 80096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50792

Middle Eastern (MID) AF: 0.00385 AC: 22 AN: 5716

European-Non Finnish (NFE) AF: 0.000337 AC: 368 AN: 1091476

Other (OTH) AF: 0.00202 AC: 119 AN: 59006

GnomAD4 genome AF: 0.00562 AC: 854 AN: 151996 Hom.: 13 Cov.: 28 AF XY: 0.00510 AC XY: 379 AN XY: 74304

African (AFR) AF: 0.0183 AC: 758 AN: 41454

American (AMR) AF: 0.00373 AC: 57 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67962

Other (OTH) AF: 0.00617 AC: 13 AN: 2108

Alfa AF: 0.00261 Hom.: 3

Bravo AF: 0.00643

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-0.22
Mutation Taster		=99/1	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: rs79480579; hg19: chr11-113561001;