rs201105968

Variant names:

• chr6-95586453-G-A
• rs201105968
• NM_024641.4:c.14G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024641.4(MANEA):​c.14G>A​(p.Arg5Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000393 in 1,604,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: MANEA NM_024641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2320208).

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.14G>A	p.Arg5Gln	missense	Exon 2 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.14G>A	p.Arg5Gln	missense	Exon 2 of 5	ENSP00000351669.4	Q5SRI9
	MANEA	ENST00000369293.6	TSL:1	c.14G>A	p.Arg5Gln	missense	Exon 2 of 2	ENSP00000358299.1	X6R7A2
	MANEA	ENST00000682663.1		c.14G>A	p.Arg5Gln	missense	Exon 2 of 5	ENSP00000507267.1	Q5SRI9

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151970 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000687 AC: 17 AN: 247536 AF XY: 0.0000748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000372 AC: 54 AN: 1452636 Hom.: 0 Cov.: 32 AF XY: 0.0000444 AC XY: 32 AN XY: 721400

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.00 AC: 0 AN: 43588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.000271 AC: 23 AN: 84986

European-Finnish (FIN) AF: 0.000338 AC: 18 AN: 53242

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5694

European-Non Finnish (NFE) AF: 0.00000903 AC: 10 AN: 1106884

Other (OTH) AF: 0.0000334 AC: 2 AN: 59912

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151970 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74232

African (AFR) AF: 0.0000242 AC: 1 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.086	T
Eigen	Benign	0.017
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.20	B
Vest4		0.54
MVP		0.29
MPC		0.29
ClinPred		0.34	T
GERP RS		3.1
Varity_R		0.34
gMVP		0.74
Mutation Taster		=75/25	polymorphism

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: rs201105968; hg19: chr6-96034329;