2-54255130-T-A

Variant names:

• chr2-54255130-T-A
• rs758496971
• NM_001003937.3:c.1022A>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.1022A>T​(p.His341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H341Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPYL6 NM_001003937.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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=0.0842849).

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.1022A>T	p.His341Leu	missense	Exon 1 of 1	NP_001003937.2	Q8N831
	ACYP2	NM_138448.4	MANE Select	c.186-49558T>A		intron	N/A	NP_612457.1	A0A140VJD7
	ACYP2	NM_001320586.2		c.405-49558T>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.1022A>T	p.His341Leu	missense	Exon 1 of 1	ENSP00000417919.2	Q8N831
	ACYP2	ENST00000394666.9	TSL:1 MANE Select	c.186-49558T>A		intron	N/A	ENSP00000378161.3	P14621
	ACYP2	ENST00000607452.6	TSL:2	c.405-49558T>A		intron	N/A	ENSP00000475986.1	U3KQL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.1
DANN	Benign	0.89
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.77
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.0090
Sift	Uncertain	0.020	D
Sift4G	Benign	0.088	T
Polyphen		0.077	B
Vest4		0.12
MutPred		0.57		Loss of disorder (P = 0.0196)
MVP		0.043
MPC		0.040
ClinPred		0.098	T
GERP RS		-1.3
Varity_R		0.17
gMVP		0.19
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs758496971; hg19: chr2-54482267;