6-95606712-C-T

Variant names:

• chr6-95606712-C-T
• rs1133503
• NM_024641.4:c.*307C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.88).
• 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: NM_024641.4. 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.*307C>T		3_prime_UTR	Exon 5 of 5	NP_078917.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	ENST00000358812.9	TSL:1 MANE Select	c.*307C>T		3_prime_UTR	Exon 5 of 5	ENSP00000351669.4	Q5SRI9
	MANEA	ENST00000682663.1		c.*307C>T		3_prime_UTR	Exon 5 of 5	ENSP00000507267.1	Q5SRI9
	MANEA	ENST00000684753.1		c.*307C>T		3_prime_UTR	Exon 5 of 5	ENSP00000506887.1	Q5SRI9

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

African (AFR) AF: 0.613 AC: 260 AN: 424

American (AMR) AF: 0.497 AC: 442 AN: 890

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 266 AN: 464

East Asian (EAS) AF: 0.827 AC: 915 AN: 1106

South Asian (SAS) AF: 0.684 AC: 405 AN: 592

European-Finnish (FIN) AF: 0.523 AC: 201 AN: 384

Middle Eastern (MID) AF: 0.581 AC: 36 AN: 62

European-Non Finnish (NFE) AF: 0.573 AC: 5698 AN: 9950

Other (OTH) AF: 0.625 AC: 464 AN: 742

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

African (AFR) AF: 0.622 AC: 25777 AN: 41430

American (AMR) AF: 0.533 AC: 8121 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2063 AN: 3464

East Asian (EAS) AF: 0.867 AC: 4469 AN: 5154

South Asian (SAS) AF: 0.732 AC: 3523 AN: 4810

European-Finnish (FIN) AF: 0.537 AC: 5644 AN: 10514

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39180 AN: 67858

Other (OTH) AF: 0.620 AC: 1306 AN: 2108

Alfa AF: 0.586 Hom.: 7260

Bravo AF: 0.597

Asia WGS AF: 0.777 AC: 2674 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.8
DANN	Benign	0.61
PhyloP100		1.1
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: rs1133503; hg19: chr6-96054588;