ENST00000369293.6:c.-169G>T

Variant names:

• chr6-95577508-G-T
• rs7755854
• ENST00000369293.6:c.-169G>T

Variant summary

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

The ENST00000369293.6(MANEA):​c.-169G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,148 control chromosomes in the GnomAD database, including 28,134 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 (28114 hom., cov: 34)
  • Exomes 𝑓: 0.64 (20 hom.)
• Consequence: MANEA ENST00000369293.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402
• Publications: 8 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]

MANEA-DT (HGNC:43732): (MANEA divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	NM_024641.4	MANE Select	c.-169G>T		upstream_gene	N/A	NP_078917.2
	MANEA-DT	NR_047502.1		n.-57C>A		upstream_gene	N/A
	MANEA-DT	NR_104136.1		n.-57C>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MANEA	ENST00000369293.6	TSL:1	c.-169G>T		5_prime_UTR	Exon 1 of 2	ENSP00000358299.1
	MANEA-DT	ENST00000791249.1		n.64+122C>A		intron	N/A
	MANEA	ENST00000358812.9	TSL:1 MANE Select	c.-169G>T		upstream_gene	N/A	ENSP00000351669.4

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91701 AN: 151944 Hom.: 28103 Cov.: 34

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.635 AC: 61 AN: 96 Hom.: 20 Cov.: 0 AF XY: 0.611 AC XY: 44 AN XY: 72

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.646 AC: 53 AN: 82

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.603 AC: 91748 AN: 152052 Hom.: 28114 Cov.: 34 AF XY: 0.601 AC XY: 44726 AN XY: 74362

African (AFR) AF: 0.642 AC: 26663 AN: 41514

American (AMR) AF: 0.536 AC: 8199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2067 AN: 3472

East Asian (EAS) AF: 0.867 AC: 4472 AN: 5158

South Asian (SAS) AF: 0.734 AC: 3544 AN: 4826

European-Finnish (FIN) AF: 0.529 AC: 5585 AN: 10550

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39212 AN: 67936

Other (OTH) AF: 0.625 AC: 1317 AN: 2106

Alfa AF: 0.576 Hom.: 3164

Bravo AF: 0.604

Asia WGS AF: 0.773 AC: 2677 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.65
PhyloP100		0.40
PromoterAI		-0.031	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7755854; hg19: chr6-96025384; COSMIC: COSV62589654;