dbSNP rs1805761: M6PR:c.-1-532A>G (chr12-8946937-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002355.4(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
NM_002355.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410

Publications

14 publications found

Variant links:

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]

M6PR links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
M6PR	NM_002355.4 link	c.-1-532A>G		intron_variant	Intron 1 of 6	ENST00000000412.8	NP_002346.1	P20645

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
M6PR	ENST00000000412.8 link	c.-1-532A>G		intron_variant	Intron 1 of 6	1	NM_002355.4	ENSP00000000412.3		P20645

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58778

AN:

151898

Hom.:

12038

Cov.:

show subpopulations

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:

AN:

136

Hom.:

AF XY:

0.419

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.625

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.438

AC:

AN:

112

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.387

AC:

58799

AN:

152016

Hom.:

12042

Cov.:

AF XY:

0.389

AC XY:

28897

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.248

AC:

10289

AN:

41480

American (AMR)

AF:

0.394

AC:

6011

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1626

AN:

3470

East Asian (EAS)

AF:

0.407

AC:

2099

AN:

5156

South Asian (SAS)

AF:

0.462

AC:

2228

AN:

4824

European-Finnish (FIN)

AF:

0.476

AC:

5018

AN:

10546

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.445

AC:

30274

AN:

67958

Other (OTH)

AF:

0.396

AC:

833

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1786

3572

5358

7144

8930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.427

Hom.:

31343

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

(source)

DANN

Benign

0.67

PhyloP100

0.041

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over