rs9374586

Positions:

• chr6-95587299-T-C
• chr6-95587299-T-G

Variant summary

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

The ENST00000358812.9(MANEA):​c.544+316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 302,378 control chromosomes in the GnomAD database, including 57,295 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 0.65 (32168 hom., cov: 31)
  • Exomes 𝑓: 0.57 (25127 hom.)
• Consequence: MANEA ENST00000358812.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

Genes affected

MANEA (HGNC:21072): (mannosidase endo-alpha) N-glycosylation of proteins is initiated in the endoplasmic reticulum (ER) by the transfer of the preassembled oligosaccharide glucose-3-mannose-9-N-acetylglucosamine-2 from dolichyl pyrophosphate to acceptor sites on the target protein by an oligosaccharyltransferase complex. This core oligosaccharide is sequentially processed by several ER glycosidases and by an endomannosidase (E.C. 3.2.1.130), such as MANEA, in the Golgi. MANEA catalyzes the release of mono-, di-, and triglucosylmannose oligosaccharides by cleaving the alpha-1,2-mannosidic bond that links them to high-mannose glycans (Hamilton et al., 2005 [PubMed 15677381]).[supplied by OMIM, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANEA	NM_024641.4	c.544+316T>C		intron_variant		ENST00000358812.9	NP_078917.2
MANEA	XM_005267147.4	c.544+316T>C		intron_variant			XP_005267204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9	c.544+316T>C		intron_variant		1	NM_024641.4	ENSP00000351669	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98248 AN: 151742 Hom.: 32156 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.574 AC: 86335 AN: 150518 Hom.: 25127 Cov.: 0 AF XY: 0.576 AC XY: 44586 AN XY: 77454

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.647 AC: 98307 AN: 151860 Hom.: 32168 Cov.: 31 AF XY: 0.645 AC XY: 47807 AN XY: 74174

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.673

Alfa AF: 0.633 Hom.: 29475

Bravo AF: 0.650

Asia WGS AF: 0.786 AC: 2730 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.75

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: rs9374586; hg19: chr6-96035175;