1-147647506-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 13/19 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034371763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP6	NM_016361.5	c.1204A>T	p.Met402Leu	missense_variant	Exon 10 of 10	ENST00000583509.7	NP_057445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP6	ENST00000583509.7	c.1204A>T	p.Met402Leu	missense_variant	Exon 10 of 10	1	NM_016361.5	ENSP00000463574.1
ACP6	ENST00000613673.4	n.4426A>T		non_coding_transcript_exon_variant	Exon 8 of 8	1
ACP6	ENST00000609196.5	c.458+2637A>T		intron_variant	Intron 5 of 5	3		ENSP00000477476.2
ACP6	ENST00000460583.1	n.767A>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251382 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135868

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 SAS 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: 23 AN: 1461818 Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0060
DANN	Benign	0.36
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.47	N
PrimateAI	Benign	0.30	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.43		Loss of phosphorylation at Y405 (P = 0.1147);
MVP		0.13
ClinPred		0.023	T
GERP RS		-6.1
Varity_R		0.12
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs114396949; hg19: chr1-147119308;