chr1-147655173-C-T

Variant names:

• chr1-147655173-C-T
• NM_016361.5:c.635G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016361.5(ACP6):​c.635G>A​(p.Arg212Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACP6 NM_016361.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0740
• Publications: 0 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: 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=0.056426138).

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.635G>A	p.Arg212Lys	missense	Exon 5 of 10	NP_057445.4
	ACP6	NM_001323625.2		c.635G>A	p.Arg212Lys	missense	Exon 5 of 9	NP_001310554.1
	ACP6	NR_136633.2		n.1111G>A		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP6	ENST00000583509.7	TSL:1 MANE Select	c.635G>A	p.Arg212Lys	missense	Exon 5 of 10	ENSP00000463574.1	Q9NPH0-1
	ACP6	ENST00000392988.6	TSL:1	c.506G>A	p.Arg169Lys	missense	Exon 4 of 6	ENSP00000376714.3	A0A0A0MS36
	ACP6	ENST00000613673.4	TSL:1	n.870G>A		non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.76
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.43	N
PhyloP100		0.074
PrimateAI	Benign	0.34	T
REVEL	Benign	0.13
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.059
MutPred		0.53		Gain of methylation at R212 (P = 0.0062)
MVP		0.23
ClinPred		0.094	T
GERP RS		-0.95
Varity_R		0.043
gMVP		0.35
Mutation Taster		=93/7	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

hg19: chr1-147127288;