chr6-95587299-T-C

Variant names:

• chr6-95587299-T-C
• rs9374586
• ENST00000369293.6:c.*263T>C

Variant summary

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

The ENST00000369293.6(MANEA):​c.*263T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 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 ENST00000369293.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 11 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=-0.91).
• 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+316T>C		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.*263T>C		3_prime_UTR	Exon 2 of 2	ENSP00000358299.1	X6R7A2
	MANEA	ENST00000358812.9	TSL:1 MANE Select	c.544+316T>C		intron	N/A	ENSP00000351669.4	Q5SRI9
	MANEA	ENST00000684211.1		c.*263T>C		3_prime_UTR	Exon 2 of 2	ENSP00000507287.1	X6R7A2

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

African (AFR) AF: 0.635 AC: 2742 AN: 4320

American (AMR) AF: 0.498 AC: 3164 AN: 6356

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2837 AN: 4898

East Asian (EAS) AF: 0.772 AC: 6539 AN: 8474

South Asian (SAS) AF: 0.672 AC: 5900 AN: 8778

European-Finnish (FIN) AF: 0.526 AC: 10461 AN: 19872

Middle Eastern (MID) AF: 0.579 AC: 368 AN: 636

European-Non Finnish (NFE) AF: 0.557 AC: 49283 AN: 88462

Other (OTH) AF: 0.578 AC: 5041 AN: 8722

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

African (AFR) AF: 0.690 AC: 28586 AN: 41442

American (AMR) AF: 0.575 AC: 8758 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3470

East Asian (EAS) AF: 0.867 AC: 4474 AN: 5160

South Asian (SAS) AF: 0.741 AC: 3561 AN: 4808

European-Finnish (FIN) AF: 0.551 AC: 5791 AN: 10508

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42629 AN: 67920

Other (OTH) AF: 0.673 AC: 1420 AN: 2110

Alfa AF: 0.634 Hom.: 35098

Bravo AF: 0.650

Asia WGS AF: 0.786 AC: 2730 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.75
PhyloP100		-1.7
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: rs9374586; hg19: chr6-96035175;