dbSNP rs114396949: ACP6:p.Met402Leu (chr1-147647506-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016361.5(ACP6):c.1204A>T(p.Met402Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ACP6
NM_016361.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Publications

1 publications found

Variant links:

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]

ACP6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034371763).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACP6	NM_016361.5	MANE Select	c.1204A>T	p.Met402Leu	missense	Exon 10 of 10	NP_057445.4
ACP6	NM_001323625.2		c.*671A>T		3_prime_UTR	Exon 9 of 9	NP_001310554.1
ACP6	NR_136633.2		n.2314A>T		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACP6	ENST00000583509.7	TSL:1 MANE Select	c.1204A>T	p.Met402Leu	missense	Exon 10 of 10	ENSP00000463574.1	Q9NPH0-1
ACP6	ENST00000613673.4	TSL:1	n.4426A>T		non_coding_transcript_exon	Exon 8 of 8
ACP6	ENST00000856437.1		c.1228A>T	p.Met410Leu	missense	Exon 10 of 10	ENSP00000526496.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251382

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0060

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.048

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.58

M_CAP

Benign

0.0068

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.47

PhyloP100

-2.4

PrimateAI

Benign

0.30

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.093

MutPred

0.43

Loss of phosphorylation at Y405 (P = 0.1147)

MVP

0.13

ClinPred

0.023

GERP RS

-6.1

Varity_R

0.12

gMVP

0.63

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over