Genetic Variant TSPYL6:p.Pro195_Leu196insGlyPro (chr2-54255566-G-GGGGCCC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BS1BS2

The NM_001003937.3(TSPYL6):c.580_585dupGGGCCC(p.Pro195_Leu196insGlyPro) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,612,674 control chromosomes in the GnomAD database, including 60 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 28)

Exomes 𝑓: 0.0015 ( 28 hom. )

Consequence

TSPYL6
NM_001003937.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 Likely_benign. Variant got -6 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001003937.3.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1637/151678) while in subpopulation AFR AF= 0.0356 (1469/41272). AF 95% confidence interval is 0.0341. There are 32 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL6	NM_001003937.3 link	c.580_585dupGGGCCC	p.Pro195_Leu196insGlyPro	conservative_inframe_insertion	Exon 1 of 1	ENST00000317802.9	NP_001003937.2	Q8N831A0A140VJY4
ACYP2	NM_001320586.2 link	c.405-49109_405-49104dupGGGCCC		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_585dupGGGCCC	p.Pro195_Leu196insGlyPro	conservative_inframe_insertion	Exon 1 of 1	6	NM_001003937.3	ENSP00000417919.2	Q8N831
ACYP2	ENST00000607452.6 link	c.405-49109_405-49104dupGGGCCC		intron_variant	Intron 6 of 6	2	NM_001320586.2	ENSP00000475986.1	U3KQL2
ACYP2	ENST00000394666.8 link	c.186-49109_186-49104dupGGGCCC		intron_variant	Intron 3 of 3	1		ENSP00000378161.3	P14621

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1635

AN:

151560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00137

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000648

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00229

AC:

560

AN:

244496

Hom.:

AF XY:

0.00192

AC XY:

256

AN XY:

133544

show subpopulations

Gnomad AFR exome

AF:

0.0253

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00162

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.000917

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000427

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.00146

AC:

2132

AN:

1460996

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

981

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.0354

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.000957

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000451

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.0108

AC:

1637

AN:

151678

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

772

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.0356

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00138

Gnomad4 SAS

AF:

0.00167

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000648

Gnomad4 OTH

AF:

0.00995

ClinVar

Not reported in ClinVar

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.

2-54255566-GGGGCCCGGGCCC-GGGGCCCGGGCCCGGGCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over