11-113688123-G-A

Position:

• chr11-113688123-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030770.4(TMPRSS5):​c.*137C>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 0.0743 in 1,345,938 control chromosomes in the GnomAD database, including 4,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1123 hom., cov: 32)
  • Exomes 𝑓: 0.071 (3386 hom.)
• Consequence: TMPRSS5 NM_030770.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.958

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-113688123-G-A is Benign according to our data. Variant chr11-113688123-G-A is described in ClinVar as [Benign]. Clinvar id is 1179359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS5	NM_030770.4	c.*137C>T		3_prime_UTR_variant	13/13	ENST00000299882.11	NP_110397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882	c.*137C>T		3_prime_UTR_variant	13/13	1	NM_030770.4	ENSP00000299882.5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15720 AN: 152138 Hom.: 1121 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0706 AC: 84217 AN: 1193682 Hom.: 3386 Cov.: 20 AF XY: 0.0697 AC XY: 40034 AN XY: 574632

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.0663

Gnomad4 ASJ exome AF: 0.0865

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.0410

Gnomad4 FIN exome AF: 0.0344

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.103 AC: 15742 AN: 152256 Hom.: 1123 Cov.: 32 AF XY: 0.0991 AC XY: 7378 AN XY: 74424

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0825 Hom.: 573

Bravo AF: 0.111

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17115826; hg19: chr11-113558845;