rs201422387

Variant names:

• chr11-113690266-C-A
• rs201422387
• NM_030770.4:c.1171G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-113690266-C-A
• chr11-113690266-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030770.4(TMPRSS5):​c.1171G>T​(p.Ala391Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000892 in 1,559,782 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00094 (3 hom.)
• Consequence: TMPRSS5 NM_030770.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.97
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034849584).
• BP6: Variant 11-113690266-C-A is Benign according to our data. Variant chr11-113690266-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1317769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 62 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.1171G>T	p.Ala391Ser	missense	Exon 11 of 13	NP_110397.2	Q9H3S3
	TMPRSS5	NM_001288751.2		c.1144G>T	p.Ala382Ser	missense	Exon 11 of 13	NP_001275680.1	F5GX83
	TMPRSS5	NM_001288750.2		c.1039G>T	p.Ala347Ser	missense	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.1171G>T	p.Ala391Ser	missense	Exon 11 of 13	ENSP00000299882.5	Q9H3S3
	TMPRSS5	ENST00000545579.6	TSL:1	c.1144G>T	p.Ala382Ser	missense	Exon 11 of 13	ENSP00000441104.1	F5GX83
	TMPRSS5	ENST00000538955.5	TSL:1	c.1039G>T	p.Ala347Ser	missense	Exon 10 of 12	ENSP00000445528.1	F5H2M3

Frequencies

GnomAD3 genomes AF: 0.000409 AC: 62 AN: 151564 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000856

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000679 AC: 115 AN: 169452 AF XY: 0.000622

Gnomad AFR exome AF: 0.000230

Gnomad AMR exome AF: 0.0000394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00190

Gnomad NFE exome AF: 0.00112

Gnomad OTH exome AF: 0.000215

GnomAD4 exome AF: 0.000944 AC: 1329 AN: 1408102 Hom.: 3 Cov.: 51 AF XY: 0.000882 AC XY: 613 AN XY: 695288

African (AFR) AF: 0.000126 AC: 4 AN: 31864

American (AMR) AF: 0.00 AC: 0 AN: 36274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25188

East Asian (EAS) AF: 0.0000276 AC: 1 AN: 36198

South Asian (SAS) AF: 0.00 AC: 0 AN: 79510

European-Finnish (FIN) AF: 0.00222 AC: 111 AN: 49922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00109 AC: 1179 AN: 1084900

Other (OTH) AF: 0.000581 AC: 34 AN: 58552

GnomAD4 genome AF: 0.000409 AC: 62 AN: 151680 Hom.: 0 Cov.: 28 AF XY: 0.000337 AC XY: 25 AN XY: 74086

African (AFR) AF: 0.0000726 AC: 3 AN: 41332

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

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

European-Finnish (FIN) AF: 0.000856 AC: 9 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000736 AC: 50 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.000682 Hom.: 1

Bravo AF: 0.000389

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000243 AC: 1

ESP6500EA AF: 0.000238 AC: 2

ExAC AF: 0.000591 AC: 69

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
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.035	T
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		6.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MVP		0.91
MPC		0.40
ClinPred		0.25	T
GERP RS		4.2
Varity_R		0.91
gMVP		0.81
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201422387; hg19: chr11-113560988; COSMIC: COSV55426484; COSMIC: COSV55426484;