Genetic Variant TSPYL6:p.Gly194_Pro195del (chr2-54255566-GGGGCCC-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The NM_001003937.3(TSPYL6):c.580_585delGGGCCC(p.Gly194_Pro195del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,612,874 control chromosomes in the GnomAD database, including 17,278 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1784 hom., cov: 28)

Exomes 𝑓: 0.14 ( 15494 hom. )

Consequence

TSPYL6
NM_001003937.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.190

Variant links:

Genes affected

TSPYL6 (HGNC:14521): (TSPY like 6) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in nucleosome assembly. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TSPYL6 links:

ACYP2 (HGNC:180): (acylphosphatase 2) Acylphosphatase can hydrolyze the phosphoenzyme intermediate of different membrane pumps, particularly the Ca2+/Mg2+-ATPase from sarcoplasmic reticulum of skeletal muscle. Two isoenzymes have been isolated, called muscle acylphosphatase and erythrocyte acylphosphatase on the basis of their tissue localization. This gene encodes the muscle-type isoform (MT). An increase of the MT isoform is associated with muscle differentiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACYP2 links:

LOC105374610 (HGNC:):

LOC105374610 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001003937.3.

BP6

Variant 2-54255566-GGGGCCC-G is Benign according to our data. Variant chr2-54255566-GGGGCCC-G is described in ClinVar as [Benign]. Clinvar id is 767796.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL6	NM_001003937.3 link	c.580_585delGGGCCC	p.Gly194_Pro195del	conservative_inframe_deletion	Exon 1 of 1	ENST00000317802.9	NP_001003937.2	Q8N831A0A140VJY4
ACYP2	NM_001320586.2 link	c.405-49109_405-49104delGGGCCC		intron_variant	Intron 6 of 6	ENST00000607452.6	NP_001307515.1	U3KQL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPYL6	ENST00000317802.9 link	c.580_585delGGGCCC	p.Gly194_Pro195del	conservative_inframe_deletion	Exon 1 of 1	6	NM_001003937.3	ENSP00000417919.2	Q8N831
ACYP2	ENST00000607452.6 link	c.405-49109_405-49104delGGGCCC		intron_variant	Intron 6 of 6	2	NM_001320586.2	ENSP00000475986.1	U3KQL2
ACYP2	ENST00000394666.8 link	c.186-49109_186-49104delGGGCCC		intron_variant	Intron 3 of 3	1		ENSP00000378161.3	P14621

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23218

AN:

151552

Hom.:

1780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.138

AC:

33849

AN:

244496

Hom.:

2447

AF XY:

0.138

AC XY:

18426

AN XY:

133544

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.0963

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.181

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.144

AC:

210440

AN:

1461204

Hom.:

15494

AF XY:

0.144

AC XY:

104552

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0993

Gnomad4 ASJ exome

AF:

0.0982

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.153

AC:

23240

AN:

151670

Hom.:

1784

Cov.:

AF XY:

0.154

AC XY:

11383

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.123

Bravo

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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