rs10165485

Variant names:

• chr2-54254499-T-C
• rs10165485
• NM_001003937.3:c.*420A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003937.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL6	NM_001003937.3	MANE Select	c.*420A>G		3_prime_UTR	Exon 1 of 1	NP_001003937.2	Q8N831
	ACYP2	NM_138448.4	MANE Select	c.186-50189T>C		intron	N/A	NP_612457.1	A0A140VJD7
	ACYP2	NM_001320586.2		c.405-50189T>C		intron	N/A	NP_001307515.1	U3KQL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL6	ENST00000317802.9	TSL:6 MANE Select	c.*420A>G		3_prime_UTR	Exon 1 of 1	ENSP00000417919.2	Q8N831
	ACYP2	ENST00000394666.9	TSL:1 MANE Select	c.186-50189T>C		intron	N/A	ENSP00000378161.3	P14621
	ACYP2	ENST00000607452.6	TSL:2	c.405-50189T>C		intron	N/A	ENSP00000475986.1	U3KQL2

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

African (AFR) AF: 0.186 AC: 45 AN: 242

American (AMR) AF: 0.0886 AC: 106 AN: 1196

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 16 AN: 260

East Asian (EAS) AF: 0.117 AC: 38 AN: 326

South Asian (SAS) AF: 0.0667 AC: 26 AN: 390

European-Finnish (FIN) AF: 0.121 AC: 34 AN: 282

Middle Eastern (MID) AF: 0.143 AC: 4 AN: 28

European-Non Finnish (NFE) AF: 0.116 AC: 750 AN: 6440

Other (OTH) AF: 0.106 AC: 58 AN: 548

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

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: 16 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9364 AN: 67984

Other (OTH) AF: 0.116 AC: 245 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.61
DANN	Benign	0.75
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10165485; hg19: chr2-54481636;