chr2-54138742-A-G

Variant names:

• chr2-54138742-A-G
• NM_138448.4:c.179A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138448.4(ACYP2):​c.179A>G​(p.Asn60Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ACYP2 NM_138448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• Publications: 0 publications found

Genes affected

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]

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=0.24353307).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138448.4. 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
	ACYP2	NM_138448.4	MANE Select	c.179A>G	p.Asn60Ser	missense	Exon 3 of 4	NP_612457.1	A0A140VJD7
	ACYP2	NM_001320586.2		c.398A>G	p.Asn133Ser	missense	Exon 6 of 7	NP_001307515.1	U3KQL2
	ACYP2	NM_001320587.2		c.305A>G	p.Asn102Ser	missense	Exon 5 of 6	NP_001307516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACYP2	ENST00000394666.9	TSL:1 MANE Select	c.179A>G	p.Asn60Ser	missense	Exon 3 of 4	ENSP00000378161.3	P14621
	ACYP2	ENST00000406041.5	TSL:1	c.179A>G	p.Asn60Ser	missense	Exon 3 of 4	ENSP00000385674.2	E9PF46
	ACYP2	ENST00000607452.6	TSL:2	c.398A>G	p.Asn133Ser	missense	Exon 6 of 7	ENSP00000475986.1	U3KQL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458782 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725812

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 43804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110860

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.014
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.89	T
PhyloP100		6.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.22
Sift	Benign	0.27	T
Sift4G	Benign	0.16	T
Polyphen		0.0060	B
Vest4		0.42
MutPred		0.44		Gain of phosphorylation at N60 (P = 0.0403)
MVP		0.30
MPC		0.0081
ClinPred		0.97	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.16
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr2-54365879;