NM_016361.5:c.1204A>G

Variant names:

• chr1-147647506-T-C
• rs114396949
• NM_016361.5:c.1204A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016361.5(ACP6):​c.1204A>G​(p.Met402Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,614,140 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M402I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0072 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (11 hom.)
• Consequence: ACP6 NM_016361.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.38
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003550917).
• BP6: Variant 1-147647506-T-C is Benign according to our data. Variant chr1-147647506-T-C is described in ClinVar as Benign. ClinVar VariationId is 711973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00717 (1092/152322) while in subpopulation AFR AF = 0.0248 (1030/41562). AF 95% confidence interval is 0.0235. There are 13 homozygotes in GnomAd4. There are 511 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016361.5. 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
	ACP6	NM_016361.5	MANE Select	c.1204A>G	p.Met402Val	missense	Exon 10 of 10	NP_057445.4
	ACP6	NM_001323625.2		c.*671A>G		3_prime_UTR	Exon 9 of 9	NP_001310554.1
	ACP6	NR_136633.2		n.2314A>G		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP6	ENST00000583509.7	TSL:1 MANE Select	c.1204A>G	p.Met402Val	missense	Exon 10 of 10	ENSP00000463574.1	Q9NPH0-1
	ACP6	ENST00000613673.4	TSL:1	n.4426A>G		non_coding_transcript_exon	Exon 8 of 8
	ACP6	ENST00000856437.1		c.1228A>G	p.Met410Val	missense	Exon 10 of 10	ENSP00000526496.1

Frequencies

GnomAD3 genomes AF: 0.00717 AC: 1092 AN: 152204 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00167 AC: 419 AN: 251382 AF XY: 0.00118

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000697 AC: 1019 AN: 1461818 Hom.: 11 Cov.: 33 AF XY: 0.000564 AC XY: 410 AN XY: 727224

African (AFR) AF: 0.0243 AC: 812 AN: 33480

American (AMR) AF: 0.00136 AC: 61 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5766

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111998

Other (OTH) AF: 0.00164 AC: 99 AN: 60392

GnomAD4 genome AF: 0.00717 AC: 1092 AN: 152322 Hom.: 13 Cov.: 32 AF XY: 0.00686 AC XY: 511 AN XY: 74476

African (AFR) AF: 0.0248 AC: 1030 AN: 41562

American (AMR) AF: 0.00268 AC: 41 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68044

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00485 Hom.: 4

Bravo AF: 0.00837

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00207 AC: 251

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.038
DANN	Benign	0.40
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		-2.4
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.053
MVP		0.13
ClinPred		0.0034	T
GERP RS		-6.1
Varity_R		0.090
gMVP		0.68
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs114396949; hg19: chr1-147119308;