rs9387522

Variant names:

• chr6-95607059-C-A
• rs9387522
• NM_024641.4:c.*654C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-95607059-C-A
• chr6-95607059-C-G
• chr6-95607059-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.*654C>A 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 151,814 control chromosomes in the GnomAD database, including 27,591 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 (27591 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MANEA NM_024641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANEA	NM_024641.4	c.*654C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000358812.9	NP_078917.2
MANEA	XM_005267147.4	c.*654C>A		3_prime_UTR_variant	Exon 5 of 5		XP_005267204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANEA	ENST00000358812.9	c.*654C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_024641.4	ENSP00000351669.4

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90802 AN: 151696 Hom.: 27577 Cov.: 31

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.615

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.598 AC: 90854 AN: 151814 Hom.: 27591 Cov.: 31 AF XY: 0.598 AC XY: 44325 AN XY: 74184

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.618

Alfa AF: 0.578 Hom.: 6028

Bravo AF: 0.597

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9387522; hg19: chr6-96054935;