6-116277312-T-C

Variant names:

• chr6-116277312-T-C
• rs1045182
• NM_003309.4:c.*1205A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

DSE Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003309.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL1	NM_003309.4	MANE Select	c.*1205A>G		3_prime_UTR	Exon 1 of 1	NP_003300.1	Q9H0U9
	DSE	NM_001322937.2		c.-54+18345T>C		intron	N/A	NP_001309866.1	Q9UL01
	DSE	NM_001322938.2		c.-54+18345T>C		intron	N/A	NP_001309867.1	Q9UL01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL1	ENST00000368608.4	TSL:6 MANE Select	c.*1205A>G		3_prime_UTR	Exon 1 of 1	ENSP00000357597.4	Q9H0U9
	DSE	ENST00000891542.1		c.-54+18345T>C		intron	N/A	ENSP00000561601.1
	DSE	ENST00000891543.1		c.-263+18345T>C		intron	N/A	ENSP00000561602.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.251 AC: 107 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.300 AC: 3 AN: 10

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.174 AC: 7238 AN: 41518

American (AMR) AF: 0.342 AC: 5227 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3315 AN: 5170

South Asian (SAS) AF: 0.496 AC: 2394 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10592

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17417 AN: 68012

Other (OTH) AF: 0.285 AC: 603 AN: 2114

Alfa AF: 0.264 Hom.: 7063

Bravo AF: 0.267

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.6
DANN	Benign	0.42
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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