1-147654322-G-A

Variant summary

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

The NM_016361.5(ACP6):c.652C>T(p.Arg218Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,876 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (14 hom., cov: 32)
  • Exomes 𝑓: 0.015 (211 hom.)
• Consequence: ACP6 NM_016361.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.39

Genes affected

ACP6 (HGNC:29609): (acid phosphatase 6, lysophosphatidic) This gene encodes a member of the histidine acid phosphatase protein family. The encoded protein hydrolyzes lysophosphatidic acid, which is involved in G protein-coupled receptor signaling, lipid raft modulation, and in balancing lipid composition within the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004639417).
• BP6: Variant 1-147654322-G-A is Benign according to our data. Variant chr1-147654322-G-A is described in ClinVar as [Benign]. Clinvar id is 218733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1593/152210) while in subpopulation NFE AF= 0.0172 (1171/68010). AF 95% confidence interval is 0.0164. There are 14 homozygotes in gnomad4. There are 739 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP6	NM_016361.5	c.652C>T	p.Arg218Trp	missense_variant	6/10	ENST00000583509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP6	ENST00000583509.7	c.652C>T	p.Arg218Trp	missense_variant	6/10	1	NM_016361.5	P1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1593 AN: 152092 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.00760

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00727

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0106 AC: 2671 AN: 251214 Hom.: 24 AF XY: 0.0114 AC XY: 1549 AN XY: 135768

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.00611

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.00737

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.0153 AC: 22421 AN: 1461666 Hom.: 211 Cov.: 30 AF XY: 0.0153 AC XY: 11145 AN XY: 727170

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00682

Gnomad4 ASJ exome AF: 0.000612

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.00742

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0105 AC: 1593 AN: 152210 Hom.: 14 Cov.: 32 AF XY: 0.00993 AC XY: 739 AN XY: 74428

Gnomad4 AFR AF: 0.00287

Gnomad4 AMR AF: 0.00759

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.00727

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0143 Hom.: 36

Bravo AF: 0.00976

TwinsUK AF: 0.0224 AC: 83

ALSPAC AF: 0.0228 AC: 88

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.0167 AC: 144

ExAC AF: 0.0109 AC: 1319

EpiCase AF: 0.0155

EpiControl AF: 0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Mar 06, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.085	T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.92	D;D;D
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	2.9	M;M;.
MutationTaster	Benign	0.57	N;N
PrimateAI	Benign	0.42	T
Sift4G	Uncertain	0.023	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.15
ClinPred		0.032	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140566115; hg19: chr1-147126437; COSMIC: COSV65076507; COSMIC: COSV65076507;