Genetic Variant NM_016361.5:c.379G>T (chr1-147659496-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_016361.5(ACP6):c.379G>T(p.Val127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. V127M) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Consequence

ACP6
NM_016361.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-147659496-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 224824.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.24794012).

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.379G>T	p.Val127Leu	missense	Exon 3 of 10	NP_057445.4
ACP6	NM_001323625.2		c.379G>T	p.Val127Leu	missense	Exon 3 of 9	NP_001310554.1
ACP6	NR_136633.2		n.855G>T		non_coding_transcript_exon	Exon 3 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACP6	ENST00000583509.7	TSL:1 MANE Select	c.379G>T	p.Val127Leu	missense	Exon 3 of 10	ENSP00000463574.1
ACP6	ENST00000392988.6	TSL:1	c.250G>T	p.Val84Leu	missense	Exon 2 of 6	ENSP00000376714.3
ACP6	ENST00000613673.4	TSL:1	n.614G>T		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251342

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.75

M_CAP

Benign

0.0066

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

1.1

PrimateAI

Benign

0.42

REVEL

Benign

0.046

Sift4G

Benign

0.20

Polyphen

0.040

Vest4

0.21

MutPred

0.53

Loss of methylation at K126 (P = 0.035)

MVP

0.26

ClinPred

0.59

GERP RS

4.7

PromoterAI

0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.49

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over