2-54255647-C-A

Variant names:

• chr2-54255647-C-A
• rs762227245
• NM_001003937.3:c.505G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001003937.3(TSPYL6):​c.505G>T​(p.Glu169*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSPYL6 NM_001003937.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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]

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]

LOC105374610 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL6	NM_001003937.3	c.505G>T	p.Glu169*	stop_gained	Exon 1 of 1	ENST00000317802.9	NP_001003937.2
ACYP2	NM_001320586.2	c.405-49041C>A		intron_variant	Intron 6 of 6	ENST00000607452.6	NP_001307515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPYL6	ENST00000317802.9	c.505G>T	p.Glu169*	stop_gained	Exon 1 of 1	6	NM_001003937.3	ENSP00000417919.2
ACYP2	ENST00000607452.6	c.405-49041C>A		intron_variant	Intron 6 of 6	2	NM_001320586.2	ENSP00000475986.1
ACYP2	ENST00000394666.8	c.186-49041C>A		intron_variant	Intron 3 of 3	1		ENSP00000378161.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248694 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135052

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461510 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Benign	0.96
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.096	N
Vest4		0.048
GERP RS		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs762227245; hg19: chr2-54482784;