Genetic Variant NM_001003937.3:c.*420A>G (chr2-54254499-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001003937.3(TSPYL6):c.*420A>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 0.142 in 161,826 control chromosomes in the GnomAD database, including 1,641 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 0.14 ( 1574 hom., cov: 32)

Exomes 𝑓: 0.11 ( 67 hom. )

Consequence

TSPYL6
NM_001003937.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.671

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL6	NM_001003937.3 link	c.*420A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000317802.9	NP_001003937.2	Q8N831A0A140VJY4
ACYP2	NM_001320586.2 link	c.405-50189T>C		intron_variant	Intron 6 of 6	ENST00000607452.6	NP_001307515.1	U3KQL2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPYL6	ENST00000317802.9 link	c.*420A>G	3_prime_UTR_variant	Exon 1 of 1	6	NM_001003937.3	ENSP00000417919.2	Q8N831
ACYP2	ENST00000607452.6 link	c.405-50189T>C	intron_variant	Intron 6 of 6	2	NM_001320586.2	ENSP00000475986.1	U3KQL2
ACYP2	ENST00000394666.9 link	c.186-50189T>C	intron_variant	Intron 3 of 3	1		ENSP00000378161.3	P14621

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21842

AN:

151996

Hom.:

1571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.111

AC:

1077

AN:

9712

Hom.:

Cov.:

AF XY:

0.109

AC XY:

542

AN XY:

4956

show subpopulations

African (AFR)

AF:

0.186

AC:

AN:

242

American (AMR)

AF:

0.0886

AC:

106

AN:

1196

Ashkenazi Jewish (ASJ)

AF:

0.0615

AC:

AN:

260

East Asian (EAS)

AF:

0.117

AC:

AN:

326

South Asian (SAS)

AF:

0.0667

AC:

AN:

390

European-Finnish (FIN)

AF:

0.121

AC:

AN:

282

Middle Eastern (MID)

AF:

0.143

AC:

AN:

European-Non Finnish (NFE)

AF:

0.116

AC:

750

AN:

6440

Other (OTH)

AF:

0.106

AC:

AN:

548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.144

AC:

21863

AN:

152114

Hom.:

1574

Cov.:

AF XY:

0.144

AC XY:

10674

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.176

AC:

7292

AN:

41484

American (AMR)

AF:

0.117

AC:

1791

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

357

AN:

3468

East Asian (EAS)

AF:

0.162

AC:

835

AN:

5168

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4816

European-Finnish (FIN)

AF:

0.124

AC:

1312

AN:

10596

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9364

AN:

67984

Other (OTH)

AF:

0.116

AC:

245

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

947

1894

2840

3787

4734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.136

Hom.:

6133

Bravo

AF:

0.145

Asia WGS

AF:

0.114

AC:

398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.61

(source)

DANN

Benign

0.75

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over