rs7757276

chr6-95594804-T-G

Variant summary

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

The NM_024641.4(MANEA):c.545-1933T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,222 control chromosomes in the GnomAD database, including 934 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 0.10 (934 hom., cov: 32)
• Consequence: MANEA NM_024641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MANEA	NM_024641.4	c.545-1933T>G		intron_variant		ENST00000358812.9
MANEA	XM_005267147.4	c.545-1933T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MANEA	ENST00000358812.9	c.545-1933T>G		intron_variant		1	NM_024641.4	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15925 AN: 152104 Hom.: 934 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0726

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15931 AN: 152222 Hom.: 934 Cov.: 32 AF XY: 0.105 AC XY: 7821 AN XY: 74426

Gnomad4 AFR AF: 0.0995

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0718

Alfa AF: 0.117 Hom.: 425

Bravo AF: 0.0963

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.88
Dann	Benign	0.49

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: rs7757276; hg19: chr6-96042680;