rs6552135

Positions:

• chr4-67963811-A-G
• chr4-67963811-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334830.11(TMPRSS11A):​c.-418T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 153,446 control chromosomes in the GnomAD database, including 15,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (15456 hom., cov: 32)
  • Exomes 𝑓: 0.55 (216 hom.)
• Consequence: TMPRSS11A ENST00000334830.11 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

Genes affected

UBA6-DT (HGNC:):

TMPRSS11A (HGNC:27954): (transmembrane serine protease 11A) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.67963811A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA6-DT	ENST00000500538.7	n.1988-98796A>G		intron_variant		1
TMPRSS11A	ENST00000334830.11	c.-418T>C		5_prime_UTR_variant	1/10	2		ENSP00000334611.7
UBA6-DT	ENST00000663060.1	n.1209-54697A>G		intron_variant
UBA6-DT	ENST00000667140.1	n.1469-54697A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61244 AN: 151956 Hom.: 15462 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.547 AC: 750 AN: 1370 Hom.: 216 Cov.: 0 AF XY: 0.569 AC XY: 387 AN XY: 680

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.395

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.403 AC: 61240 AN: 152076 Hom.: 15456 Cov.: 32 AF XY: 0.398 AC XY: 29590 AN XY: 74320

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.392

Alfa AF: 0.493 Hom.: 2864

Bravo AF: 0.377

Asia WGS AF: 0.392 AC: 1352 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.77

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: rs6552135; hg19: chr4-68829529;