6-95588040-C-T

Variant names:

• chr6-95588040-C-T
• rs6940020
• ENST00000369293.6:c.*1004C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369293.6(MANEA):​c.*1004C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,828 control chromosomes in the GnomAD database, including 27,497 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 0.60 (27497 hom., cov: 32)
• Consequence: MANEA ENST00000369293.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369293.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	NM_024641.4	MANE Select	c.544+1057C>T		intron	N/A	NP_078917.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	ENST00000369293.6	TSL:1	c.*1004C>T		3_prime_UTR	Exon 2 of 2	ENSP00000358299.1	X6R7A2
	MANEA	ENST00000358812.9	TSL:1 MANE Select	c.544+1057C>T		intron	N/A	ENSP00000351669.4	Q5SRI9
	MANEA	ENST00000684211.1		c.*1004C>T		3_prime_UTR	Exon 2 of 2	ENSP00000507287.1	X6R7A2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90627 AN: 151710 Hom.: 27483 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.597 AC: 90679 AN: 151828 Hom.: 27497 Cov.: 32 AF XY: 0.596 AC XY: 44212 AN XY: 74178

African (AFR) AF: 0.622 AC: 25786 AN: 41426

American (AMR) AF: 0.533 AC: 8131 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3470

East Asian (EAS) AF: 0.867 AC: 4488 AN: 5174

South Asian (SAS) AF: 0.733 AC: 3537 AN: 4826

European-Finnish (FIN) AF: 0.531 AC: 5583 AN: 10520

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39091 AN: 67850

Other (OTH) AF: 0.619 AC: 1308 AN: 2112

Alfa AF: 0.589 Hom.: 13708

Bravo AF: 0.597

Asia WGS AF: 0.775 AC: 2690 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.40
PhyloP100		1.2
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: rs6940020; hg19: chr6-96035916;