Genetic Variant NM_001003937.3:c.505G>A (chr2-54255647-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003937.3(TSPYL6):c.505G>A(p.Glu169Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 0.0000048 ( 0 hom. )

Consequence

TSPYL6
NM_001003937.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.395

Variant links:

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]

TSPYL6 links:

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]

ACYP2 links:

LOC105374610 (HGNC:):

LOC105374610 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077340364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL6	NM_001003937.3 link	c.505G>A	p.Glu169Lys	missense_variant	Exon 1 of 1	ENST00000317802.9	NP_001003937.2	Q8N831A0A140VJY4
ACYP2	NM_001320586.2 link	c.405-49041C>T		intron_variant	Intron 6 of 6	ENST00000607452.6	NP_001307515.1	U3KQL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSPYL6	ENST00000317802.9 link	c.505G>A	p.Glu169Lys	missense_variant	Exon 1 of 1	6	NM_001003937.3	ENSP00000417919.2	Q8N831
ACYP2	ENST00000607452.6 link	c.405-49041C>T		intron_variant	Intron 6 of 6	2	NM_001320586.2	ENSP00000475986.1	U3KQL2
ACYP2	ENST00000394666.8 link	c.186-49041C>T		intron_variant	Intron 3 of 3	1		ENSP00000378161.3	P14621

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.8

DANN

Benign

0.94

DEOGEN2

Benign

0.0060

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.40

M_CAP

Benign

0.0020

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.75

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.14

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.12

MutPred

0.26

Gain of ubiquitination at E169 (P = 0.0042);

MVP

0.043

MPC

0.051

ClinPred

0.13

GERP RS

-0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over