rs67497537

Positions:

• chr16-8812590-G-A
• chr16-8812590-G-C

Variant summary

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

The NM_000303.3(PMM2):​c.524-401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,008 control chromosomes in the GnomAD database, including 4,191 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 0.22 (4191 hom., cov: 33)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

Genes affected

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMM2	NM_000303.3	c.524-401G>A		intron_variant		ENST00000268261.9	NP_000294.1
PMM2	XM_047434215.1	c.275-401G>A		intron_variant			XP_047290171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMM2	ENST00000268261.9	c.524-401G>A		intron_variant		1	NM_000303.3	ENSP00000268261	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33559 AN: 151890 Hom.: 4189 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33566 AN: 152008 Hom.: 4191 Cov.: 33 AF XY: 0.226 AC XY: 16816 AN XY: 74280

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.227

Alfa AF: 0.152 Hom.: 370

Bravo AF: 0.204

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.62

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: rs67497537; hg19: chr16-8906447;