rs3785176

Variant names:

• chr16-8803074-A-C
• rs3785176
• NM_000303.3:c.178+1164A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-8803074-A-C
• chr16-8803074-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

PMM2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation type I

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• PMM2-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000303.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMM2	NM_000303.3	MANE Select	c.178+1164A>C		intron	N/A	NP_000294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMM2	ENST00000268261.9	TSL:1 MANE Select	c.178+1164A>C		intron	N/A	ENSP00000268261.4
	PMM2	ENST00000565221.5	TSL:1	n.178+1164A>C		intron	N/A	ENSP00000457932.1
	PMM2	ENST00000566540.5	TSL:1	n.178+1164A>C		intron	N/A	ENSP00000454284.1

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

African (AFR) AF: 0.107 AC: 4434 AN: 41506

American (AMR) AF: 0.139 AC: 2132 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3466

East Asian (EAS) AF: 0.264 AC: 1361 AN: 5154

South Asian (SAS) AF: 0.134 AC: 646 AN: 4816

European-Finnish (FIN) AF: 0.357 AC: 3763 AN: 10538

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17287 AN: 67972

Other (OTH) AF: 0.184 AC: 388 AN: 2110

Alfa AF: 0.219 Hom.: 6542

Bravo AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3785176; hg19: chr16-8896931;