2-54255805-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001003937.3(TSPYL6):c.347C>T(p.Pro116Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,778 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0085 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (27 hom.)
• Consequence: TSPYL6 NM_001003937.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027159154).
• BP6: Variant 2-54255805-G-A is Benign according to our data. Variant chr2-54255805-G-A is described in ClinVar as [Benign]. Clinvar id is 767797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00846 (1287/152168) while in subpopulation AFR AF= 0.0298 (1237/41532). AF 95% confidence interval is 0.0284. There are 18 homozygotes in gnomad4. There are 607 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPYL6	NM_001003937.3	c.347C>T	p.Pro116Leu	missense_variant	1/1	ENST00000317802.9
ACYP2	NM_001320586.2	c.405-48883G>A		intron_variant		ENST00000607452.6
LOC105374610	XR_007086321.1	n.1296-16521C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPYL6	ENST00000317802.9	c.347C>T	p.Pro116Leu	missense_variant	1/1		NM_001003937.3	P1
ACYP2	ENST00000607452.6	c.405-48883G>A		intron_variant		2	NM_001320586.2

Frequencies

GnomAD3 genomes AF: 0.00842 AC: 1280 AN: 152050 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00225 AC: 561 AN: 249330 Hom.: 10 AF XY: 0.00180 AC XY: 243 AN XY: 135316

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000660

GnomAD4 exome AF: 0.000857 AC: 1253 AN: 1461610 Hom.: 27 Cov.: 33 AF XY: 0.000754 AC XY: 548 AN XY: 727134

Gnomad4 AFR exome AF: 0.0318

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00846 AC: 1287 AN: 152168 Hom.: 18 Cov.: 32 AF XY: 0.00816 AC XY: 607 AN XY: 74404

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00407 Hom.: 2

Bravo AF: 0.00969

ESP6500AA AF: 0.0276 AC: 113

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00279 AC: 337

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.34
Dann	Benign	0.82
DEOGEN2	Benign	0.00067	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.012
Sift	Benign	0.15	T
Sift4G	Benign	0.37	T
Polyphen		0.0020	B
Vest4		0.10
MVP		0.043
MPC		0.019
ClinPred		0.0010	T
GERP RS		-2.2
Varity_R		0.021
gMVP		0.034

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

Other links and lift over

dbSNP: rs13424808; hg19: chr2-54482942; COSMIC: COSV57816706;