2-54255600-G-A

Variant names:

• chr2-54255600-G-A
• rs754452381
• NM_001003937.3:c.552C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001003937.3(TSPYL6):​c.552C>T​(p.Asn184Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TSPYL6 NM_001003937.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-2.47 with no splicing effect.

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.552C>T	p.Asn184Asn	synonymous	Exon 1 of 1	NP_001003937.2	Q8N831
	ACYP2	NM_138448.4	MANE Select	c.186-49088G>A		intron	N/A	NP_612457.1	A0A140VJD7
	ACYP2	NM_001320586.2		c.405-49088G>A		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.552C>T	p.Asn184Asn	synonymous	Exon 1 of 1	ENSP00000417919.2	Q8N831
	ACYP2	ENST00000394666.9	TSL:1 MANE Select	c.186-49088G>A		intron	N/A	ENSP00000378161.3	P14621
	ACYP2	ENST00000607452.6	TSL:2	c.405-49088G>A		intron	N/A	ENSP00000475986.1	U3KQL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247400 AF XY: 0.00000743

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461408 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.67
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs754452381; hg19: chr2-54482737;