chr11-113690262-C-T

Variant names:

• chr11-113690262-C-T
• rs528227924
• NM_030770.4:c.1175G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_030770.4(TMPRSS5):​c.1175G>A​(p.Gly392Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000712 in 1,404,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMPRSS5 NM_030770.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS5	NM_030770.4	c.1175G>A	p.Gly392Asp	missense_variant	Exon 11 of 13	ENST00000299882.11	NP_110397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11	c.1175G>A	p.Gly392Asp	missense_variant	Exon 11 of 13	1	NM_030770.4	ENSP00000299882.5

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD3 exomes AF: 0.00000600 AC: 1 AN: 166802 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 88664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000434

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404142 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 693218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D;D;D;D;.;D;D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	.;D;D;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Pathogenic	3.3	M;M;.;.;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.6	.;D;D;D;D;D;D;D
REVEL	Pathogenic	0.74
Sift	Benign	0.032	.;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	.;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;.;D;.
Vest4		0.58, 0.48, 0.41, 0.49, 0.49, 0.49
MutPred		0.96		Loss of methylation at R397 (P = 0.0954);Loss of methylation at R397 (P = 0.0954);.;.;.;.;.;.;
MVP		0.95
MPC		0.43
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.91
gMVP		0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs528227924; hg19: chr11-113560984;