6-95577508-G-T

Variant names:

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

Variant summary

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

The ENST00000369293(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 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANEA	NM_024641.4	c.-169G>T		upstream_gene_variant		ENST00000358812.9	NP_078917.2
MANEA-DT	NR_047502.1	n.-57C>A		upstream_gene_variant
MANEA-DT	NR_104136.1	n.-57C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9	c.-169G>T		upstream_gene_variant		1	NM_024641.4	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

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.625

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

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