6-95606712-C-T

Position:

• chr6-95606712-C-T

Variant summary

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

The NM_024641.4(MANEA):​c.*307C>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 0.598 in 166,386 control chromosomes in the GnomAD database, including 30,217 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 (27554 hom., cov: 31)
  • Exomes 𝑓: 0.59 (2663 hom.)
• Consequence: MANEA NM_024641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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=-0.88).
• 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.*307C>T		3_prime_UTR_variant	5/5	ENST00000358812.9	NP_078917.2
MANEA	XM_005267147.4	c.*307C>T		3_prime_UTR_variant	5/5		XP_005267204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9	c.*307C>T		3_prime_UTR_variant	5/5	1	NM_024641.4	ENSP00000351669	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90721 AN: 151654 Hom.: 27540 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.594 AC: 8687 AN: 14614 Hom.: 2663 Cov.: 0 AF XY: 0.588 AC XY: 4703 AN XY: 8000

Gnomad4 AFR exome AF: 0.613

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.827

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.598 AC: 90773 AN: 151772 Hom.: 27554 Cov.: 31 AF XY: 0.597 AC XY: 44279 AN XY: 74184

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.620

Alfa AF: 0.583 Hom.: 6270

Bravo AF: 0.597

Asia WGS AF: 0.777 AC: 2674 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.8
DANN	Benign	0.61

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: rs1133503; hg19: chr6-96054588;