Variant 6-116279302-T-TCAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_003309.4(TSPYL1):c.528_529insGTG(p.Val176dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,609,234 control chromosomes in the GnomAD database, including 386,893 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 45285 hom., cov: 0)

Exomes 𝑓: 0.68 ( 341608 hom. )

Consequence

TSPYL1
NM_003309.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.225

Variant links:

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]

TSPYL1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_003309.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 6-116279302-T-TCAC is Benign according to our data. Variant chr6-116279302-T-TCAC is described in ClinVar as [Benign]. Clinvar id is 1301648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPYL1	NM_003309.4 linkuse as main transcript	c.528_529insGTG	p.Val176dup	inframe_insertion	1/1	ENST00000368608.4	NP_003300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPYL1	ENST00000368608.4 linkuse as main transcript	c.528_529insGTG	p.Val176dup	inframe_insertion	1/1		NM_003309.4	ENSP00000357597	P1

Frequencies

GnomAD3 genomes

AF:

0.761

AC:

115322

AN:

151600

Hom.:

45227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.696

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.931

Gnomad FIN

AF:

0.761

Gnomad MID

AF:

0.657

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.720

GnomAD4 exome

AF:

0.676

AC:

985557

AN:

1457516

Hom.:

341608

Cov.:

AF XY:

0.682

AC XY:

494778

AN XY:

725246

show subpopulations

Gnomad4 AFR exome

AF:

0.931

Gnomad4 AMR exome

AF:

0.826

Gnomad4 ASJ exome

AF:

0.682

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.914

Gnomad4 FIN exome

AF:

0.757

Gnomad4 NFE exome

AF:

0.627

Gnomad4 OTH exome

AF:

0.697

GnomAD4 genome

AF:

0.761

AC:

115440

AN:

151718

Hom.:

45285

Cov.:

AF XY:

0.771

AC XY:

57141

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.922

Gnomad4 AMR

AF:

0.763

Gnomad4 ASJ

AF:

0.696

Gnomad4 EAS

AF:

0.996

Gnomad4 SAS

AF:

0.930

Gnomad4 FIN

AF:

0.761

Gnomad4 NFE

AF:

0.639

Gnomad4 OTH

AF:

0.724

Alfa

AF:

0.695

Hom.:

6185

Asia WGS

AF:

0.948

AC:

3296

AN:

3478

EpiCase

AF:

0.629

EpiControl

AF:

0.631

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Ehlers-Danlos syndrome, musculocontractural type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Apr 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over