4-102726614-C-G

Variant names:

• chr4-102726614-C-G
• rs121434335
• NM_005908.4:c.247G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005908.4(MANBA):​c.247G>C​(p.Glu83Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MANBA NM_005908.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

Genes affected

MANBA (HGNC:6831): (mannosidase beta) This gene encodes a member of the glycosyl hydrolase 2 family. The encoded protein localizes to the lysosome where it is the final exoglycosidase in the pathway for N-linked glycoprotein oligosaccharide catabolism. Mutations in this gene are associated with beta-mannosidosis, a lysosomal storage disease that has a wide spectrum of neurological involvement. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13255197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MANBA	NM_005908.4	c.247G>C	p.Glu83Gln	missense_variant	Exon 2 of 17	ENST00000647097.2	NP_005899.3
MANBA	XM_047415692.1	c.172G>C	p.Glu58Gln	missense_variant	Exon 3 of 18		XP_047271648.1
MANBA	XM_047415693.1	c.172G>C	p.Glu58Gln	missense_variant	Exon 3 of 18		XP_047271649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MANBA	ENST00000647097.2	c.247G>C	p.Glu83Gln	missense_variant	Exon 2 of 17		NM_005908.4	ENSP00000495247.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.24	.;T;T;.;.;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.84	T;.;T;D;D;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	.;L;L;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.62	.;N;.;.;N;.
REVEL	Benign	0.014
Sift	Benign	0.32	.;T;.;.;T;.
Sift4G	Benign	0.47	.;T;.;.;T;.
Polyphen		0.075, 0.024	.;B;B;.;B;.
Vest4		0.26, 0.26
MutPred		0.40		Gain of MoRF binding (P = 0.0733);Gain of MoRF binding (P = 0.0733);Gain of MoRF binding (P = 0.0733);Gain of MoRF binding (P = 0.0733);Gain of MoRF binding (P = 0.0733);.;
MVP		0.36
MPC		0.088
ClinPred		0.053	T
GERP RS		1.5
Varity_R		0.055
gMVP		0.35

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: rs121434335; hg19: chr4-103647771; COSMIC: COSV56963551; COSMIC: COSV56963551;