rs1805762

Positions:

• chr12-8945306-C-G
• chr12-8945306-C-T

Variant summary

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

The NM_002355.4(M6PR):​c.343+112G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,122,512 control chromosomes in the GnomAD database, including 2,708 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 0.046 (312 hom., cov: 33)
  • Exomes 𝑓: 0.057 (2396 hom.)
• Consequence: M6PR NM_002355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
M6PR	NM_002355.4	c.343+112G>C		intron_variant		ENST00000000412.8	NP_002346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
M6PR	ENST00000000412.8	c.343+112G>C		intron_variant		1	NM_002355.4	ENSP00000000412	P1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7072 AN: 152124 Hom.: 314 Cov.: 33

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0693

GnomAD4 exome AF: 0.0573 AC: 55603 AN: 970270 Hom.: 2396 Cov.: 13 AF XY: 0.0563 AC XY: 27800 AN XY: 493578

Gnomad4 AFR exome AF: 0.00966

Gnomad4 AMR exome AF: 0.0428

Gnomad4 ASJ exome AF: 0.0633

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.0229

Gnomad4 FIN exome AF: 0.0328

Gnomad4 NFE exome AF: 0.0548

Gnomad4 OTH exome AF: 0.0577

GnomAD4 genome AF: 0.0464 AC: 7062 AN: 152242 Hom.: 312 Cov.: 33 AF XY: 0.0475 AC XY: 3537 AN XY: 74432

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0177 Hom.: 7

Bravo AF: 0.0486

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1805762; hg19: chr12-9097902; COSMIC: COSV50003078; COSMIC: COSV50003078;