2-54255596-C-T

Position:

chr2-54255596-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001003937.3(TSPYL6):c.556G>A(p.Glu186Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,613,504 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

TSPYL6
NM_001003937.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.177

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021625519).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPYL6	NM_001003937.3 linkuse as main transcript	c.556G>A	p.Glu186Lys	missense_variant	1/1	ENST00000317802.9	NP_001003937.2	Q8N831A0A140VJY4
ACYP2	NM_001320586.2 linkuse as main transcript	c.405-49092C>T		intron_variant		ENST00000607452.6	NP_001307515.1	U3KQL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPYL6	ENST00000317802.9 linkuse as main transcript	c.556G>A	p.Glu186Lys	missense_variant	1/1	6	NM_001003937.3	ENSP00000417919.2	Q8N831
ACYP2	ENST00000607452.6 linkuse as main transcript	c.405-49092C>T		intron_variant		2	NM_001320586.2	ENSP00000475986.1	U3KQL2
ACYP2	ENST00000394666.8 linkuse as main transcript	c.186-49092C>T		intron_variant		1		ENSP00000378161.3	P14621

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000137

AC:

AN:

247282

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134516

show subpopulations

Gnomad AFR exome

AF:

0.0000657

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000155

AC:

227

AN:

1461516

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

126

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000118

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.000102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.000124

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.556G>A (p.E186K) alteration is located in exon 1 (coding exon 1) of the TSPYL6 gene. This alteration results from a G to A substitution at nucleotide position 556, causing the glutamic acid (E) at amino acid position 186 to be replaced by a lysine (K). 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

0.084

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.1

DANN

Benign

0.85

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.35

M_CAP

Benign

0.0012

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

REVEL

Benign

0.034

Sift

Benign

0.41

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.066

MVP

0.043

MPC

0.020

ClinPred

0.0068

GERP RS

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.033

gMVP

0.38

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over