rs17053466

chr9-87774422-G-A

Variant summary

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

The NR_027917.1(CTSL3P):n.425+778G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,534 control chromosomes in the GnomAD database, including 158 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 0.028 (158 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: CTSL3P NR_027917.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

Genes affected

CTSL3P (HGNC:33132): (cathepsin L family member 3, pseudogene) Predicted to enable cysteine-type endopeptidase activity. Predicted to be involved in proteolysis involved in cellular protein catabolic process. Predicted to be active in extracellular space and lysosome. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSL3P	NR_027917.1	n.425+778G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSL3P	ENST00000354530.2	n.425+778G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4259 AN: 151982 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0349

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0288

GnomAD4 exome AF: 0.00691 AC: 3 AN: 434 Hom.: 0 AF XY: 0.0115 AC XY: 3 AN XY: 260

Gnomad4 FIN exome AF: 0.00704

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0281 AC: 4273 AN: 152100 Hom.: 158 Cov.: 32 AF XY: 0.0292 AC XY: 2168 AN XY: 74366

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.0692

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.00359

Gnomad4 NFE AF: 0.00277

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.0248 Hom.: 24

Bravo AF: 0.0341

Asia WGS AF: 0.0180 AC: 63 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.75
Dann	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17053466; hg19: chr9-90389337;