6-95588040-C-T

Position:

• chr6-95588040-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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+1057C>T		intron_variant		ENST00000358812.9	NP_078917.2
MANEA	XM_005267147.4	c.544+1057C>T		intron_variant			XP_005267204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9	c.544+1057C>T		intron_variant		1	NM_024641.4	ENSP00000351669	P1

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

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.619

Alfa AF: 0.589 Hom.: 12237

Bravo AF: 0.597

Asia WGS AF: 0.775 AC: 2690 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.40

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: rs6940020; hg19: chr6-96035916;