11-113688329-G-A

Position:

• chr11-113688329-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000299882.11(TMPRSS5):​c.1360-55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,276,232 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (6 hom.)
• Consequence: TMPRSS5 ENST00000299882.11 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.465

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-113688329-G-A is Benign according to our data. Variant chr11-113688329-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00755 (1149/152254) while in subpopulation AFR AF= 0.0259 (1076/41528). AF 95% confidence interval is 0.0246. There are 14 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS5	NM_030770.4	c.1360-55C>T		intron_variant		ENST00000299882.11	NP_110397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11	c.1360-55C>T		intron_variant		1	NM_030770.4	ENSP00000299882	P2

Frequencies

GnomAD3 genomes AF: 0.00753 AC: 1145 AN: 152136 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00327

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: 0.000206

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000790 AC: 888 AN: 1123978 Hom.: 6 AF XY: 0.000651 AC XY: 369 AN XY: 567172

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.00194

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000550

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000796

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00755 AC: 1149 AN: 152254 Hom.: 14 Cov.: 32 AF XY: 0.00787 AC XY: 586 AN XY: 74450

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00338 Hom.: 1

Bravo AF: 0.00890

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.35

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: rs114930010; hg19: chr11-113559051;