rs3785176

chr16-8803074-A-Cchr16-8803074-A-T

Variant summary

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

The NM_000303.3(PMM2):c.178+1164A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,048 control chromosomes in the GnomAD database, including 3,569 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 0.20 (3569 hom., cov: 31)
• Consequence: PMM2 NM_000303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMM2	NM_000303.3	c.178+1164A>C		intron_variant		ENST00000268261.9
PMM2	XM_047434215.1	c.6+1164A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMM2	ENST00000268261.9	c.178+1164A>C		intron_variant		1	NM_000303.3	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30878 AN: 151930 Hom.: 3566 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.203 AC: 30892 AN: 152048 Hom.: 3569 Cov.: 31 AF XY: 0.204 AC XY: 15171 AN XY: 74308

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.184

Alfa AF: 0.223 Hom.: 5315

Bravo AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.5
Dann	Benign	0.45

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: rs3785176; hg19: chr16-8896931;