chr2-54254499-T-C

Position:

• chr2-54254499-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
TSPYL6	NM_001003937.3	c.*420A>G		3_prime_UTR_variant	1/1	ENST00000317802.9	NP_001003937.2
ACYP2	NM_001320586.2	c.405-50189T>C		intron_variant		ENST00000607452.6	NP_001307515.1
LOC105374610	XR_007086321.1	n.1296-15215A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPYL6	ENST00000317802.9	c.*420A>G		3_prime_UTR_variant	1/1		NM_001003937.3	ENSP00000417919	P1
ACYP2	ENST00000607452.6	c.405-50189T>C		intron_variant		2	NM_001320586.2	ENSP00000475986

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21842 AN: 151996 Hom.: 1571 Cov.: 32

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.: 67 Cov.: 0 AF XY: 0.109 AC XY: 542 AN XY: 4956

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0886

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.144 AC: 21863 AN: 152114 Hom.: 1574 Cov.: 32 AF XY: 0.144 AC XY: 10674 AN XY: 74356

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.116

Alfa AF: 0.132 Hom.: 2826

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
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs10165485; hg19: chr2-54481636;