chr6-116279302-T-TCAC

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_003309.4(TSPYL1):c.526_528dupGTG(p.Val176dup) variant causes a conservative 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 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.225

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome, musculocontractural type 2
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
Ehlers-Danlos syndrome, musculocontractural type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DSE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TSPYL1	NM_003309.4 link	c.526_528dupGTG	p.Val176dup	conservative_inframe_insertion	Exon 1 of 1	ENST00000368608.4	NP_003300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPYL1	ENST00000368608.4 link	c.526_528dupGTG	p.Val176dup	conservative_inframe_insertion	Exon 1 of 1	6	NM_003309.4	ENSP00000357597.4

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

African (AFR)

AF:

0.931

AC:

31176

AN:

33476

American (AMR)

AF:

0.826

AC:

36923

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

17832

AN:

26136

East Asian (EAS)

AF:

0.999

AC:

39649

AN:

39700

South Asian (SAS)

AF:

0.914

AC:

78799

AN:

86258

European-Finnish (FIN)

AF:

0.757

AC:

37225

AN:

49142

Middle Eastern (MID)

AF:

0.735

AC:

4241

AN:

5768

European-Non Finnish (NFE)

AF:

0.627

AC:

697611

AN:

1111944

Other (OTH)

AF:

0.697

AC:

42101

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

22013

44025

66038

88050

110063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18764

37528

56292

75056

93820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.761

AC:

115440

AN:

151718

Hom.:

45285

Cov.:

AF XY:

0.771

AC XY:

57141

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.922

AC:

38176

AN:

41396

American (AMR)

AF:

0.763

AC:

11639

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.696

AC:

2418

AN:

3472

East Asian (EAS)

AF:

0.996

AC:

5115

AN:

5134

South Asian (SAS)

AF:

0.930

AC:

4462

AN:

4796

European-Finnish (FIN)

AF:

0.761

AC:

7981

AN:

10492

Middle Eastern (MID)

AF:

0.672

AC:

195

AN:

290

European-Non Finnish (NFE)

AF:

0.639

AC:

43343

AN:

67864

Other (OTH)

AF:

0.724

AC:

1524

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1271

2542

3813

5084

6355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ehlers-Danlos syndrome, musculocontractural type 2

Benign:1

Apr 02, 2020

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.23

Mutation Taster

=81/19

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over