6-116277312-T-C

Position:

• chr6-116277312-T-C

Variant summary

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

The NM_003309.4(TSPYL1):​c.*1205A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,648 control chromosomes in the GnomAD database, including 6,070 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 0.26 (6058 hom., cov: 33)
  • Exomes 𝑓: 0.25 (12 hom.)
• Consequence: TSPYL1 NM_003309.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

Genes affected

TSPYL1 (HGNC:12382): (TSPY like 1) The protein encoded by this gene is found in the nucleolus and is similar to that of a family of genes on the Y-chromosome. This gene is intronless. Defects in this gene are a cause of sudden infant death with dysgenesis of the testes syndrome (SIDDT). [provided by RefSeq, Dec 2009]

DSE (HGNC:21144): (dermatan sulfate epimerase) The protein encoded by this gene is a tumor-rejection antigen. It is localized to the endoplasmic reticulum and functions to convert D-glucuronic acid to L-iduronic acid during the biosynthesis of dermatan sulfate. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. Mutations in this gene cause inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 9, and a paralogous gene exists on chromosome 18. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPYL1	NM_003309.4	c.*1205A>G		3_prime_UTR_variant	1/1	ENST00000368608.4	NP_003300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPYL1	ENST00000368608.4	c.*1205A>G		3_prime_UTR_variant	1/1		NM_003309.4	ENSP00000357597	P1
DSE	ENST00000430252.6	c.-54+18345T>C		intron_variant		2		ENSP00000397597
DSE	ENST00000647244.1	c.-54+18345T>C		intron_variant				ENSP00000495184
TSPYL1	ENST00000652202.1	c.*488+717A>G		intron_variant, NMD_transcript_variant				ENSP00000498597

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40018 AN: 152090 Hom.: 6050 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.251 AC: 111 AN: 442 Hom.: 12 Cov.: 0 AF XY: 0.256 AC XY: 68 AN XY: 266

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.263 AC: 40058 AN: 152206 Hom.: 6058 Cov.: 33 AF XY: 0.269 AC XY: 20043 AN XY: 74398

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.285

Alfa AF: 0.266 Hom.: 5517

Bravo AF: 0.267

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.6
DANN	Benign	0.42

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: rs1045182; hg19: chr6-116598475; COSMIC: COSV63994008; COSMIC: COSV63994008;