2-54254968-A-T

Position:

• chr2-54254968-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003937.3(TSPYL6):​c.1184T>A​(p.Val395Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPYL6 NM_001003937.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.455

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046346575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPYL6	NM_001003937.3	c.1184T>A	p.Val395Glu	missense_variant	1/1	ENST00000317802.9	NP_001003937.2
ACYP2	NM_001320586.2	c.405-49720A>T		intron_variant		ENST00000607452.6	NP_001307515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPYL6	ENST00000317802.9	c.1184T>A	p.Val395Glu	missense_variant	1/1	6	NM_001003937.3	ENSP00000417919.2
ACYP2	ENST00000607452.6	c.405-49720A>T		intron_variant		2	NM_001320586.2	ENSP00000475986.1
ACYP2	ENST00000394666.8	c.186-49720A>T		intron_variant		1		ENSP00000378161.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.1184T>A (p.V395E) alteration is located in exon 1 (coding exon 1) of the TSPYL6 gene. This alteration results from a T to A substitution at nucleotide position 1184, causing the valine (V) at amino acid position 395 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.012
Sift	Benign	0.72	T
Sift4G	Benign	0.083	T
Polyphen		0.037	B
Vest4		0.15
MutPred		0.37		Gain of disorder (P = 0.0032);
MVP		0.043
MPC		0.022
ClinPred		0.076	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-54482105;