2-54255267-C-A

Variant names:

• chr2-54255267-C-A
• rs191487480
• NM_001003937.3:c.885G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003937.3(TSPYL6):​c.885G>T​(p.Lys295Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSPYL6 NM_001003937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18496686).

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.885G>T	p.Lys295Asn	missense	Exon 1 of 1	NP_001003937.2	Q8N831
	ACYP2	NM_138448.4	MANE Select	c.186-49421C>A		intron	N/A	NP_612457.1	A0A140VJD7
	ACYP2	NM_001320586.2		c.405-49421C>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.885G>T	p.Lys295Asn	missense	Exon 1 of 1	ENSP00000417919.2	Q8N831
	ACYP2	ENST00000394666.9	TSL:1 MANE Select	c.186-49421C>A		intron	N/A	ENSP00000378161.3	P14621
	ACYP2	ENST00000607452.6	TSL:2	c.405-49421C>A		intron	N/A	ENSP00000475986.1	U3KQL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.67
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.069
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.019	D
Polyphen		0.24	B
Vest4		0.27
MutPred		0.55		Loss of methylation at K295 (P = 0.0144)
MVP		0.043
MPC		0.070
ClinPred		0.99	D
GERP RS		-0.37
Varity_R		0.59
gMVP		0.19
Mutation Taster		=89/11	polymorphism

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: rs191487480; hg19: chr2-54482404;