rs1805761

Positions:

• chr12-8946937-T-C
• chr12-8946937-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000000412.8(M6PR):​c.-1-532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,152 control chromosomes in the GnomAD database, including 12,057 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (12042 hom., cov: 32)
  • Exomes 𝑓: 0.46 (15 hom.)
• Consequence: M6PR ENST00000000412.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

Genes affected

M6PR (HGNC:6752): (mannose-6-phosphate receptor, cation dependent) This gene encodes a member of the P-type lectin family. P-type lectins play a critical role in lysosome function through the specific transport of mannose-6-phosphate-containing acid hydrolases from the Golgi complex to lysosomes. The encoded protein functions as a homodimer and requires divalent cations for ligand binding. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome X. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
M6PR	NM_002355.4	c.-1-532A>G		intron_variant		ENST00000000412.8	NP_002346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
M6PR	ENST00000000412.8	c.-1-532A>G		intron_variant		1	NM_002355.4	ENSP00000000412	P1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58778 AN: 151898 Hom.: 12038 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.456 AC: 62 AN: 136 Hom.: 15 AF XY: 0.419 AC XY: 31 AN XY: 74

Gnomad4 AMR exome AF: 0.625

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.387 AC: 58799 AN: 152016 Hom.: 12042 Cov.: 32 AF XY: 0.389 AC XY: 28897 AN XY: 74320

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.396

Alfa AF: 0.439 Hom.: 20910

Bravo AF: 0.376

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.67

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: rs1805761; hg19: chr12-9099533;