4-6575344-T-G

Variant names:

• chr4-6575344-T-G
• rs890500719
• NM_015274.3:c.134T>G

Variant summary

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

The NM_015274.3(MAN2B2):​c.134T>G​(p.Val45Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAN2B2 NM_015274.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20

Genes affected

MAN2B2 (HGNC:29623): (mannosidase alpha class 2B member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in mannose metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2B2	NM_015274.3	c.134T>G	p.Val45Gly	missense_variant	Exon 1 of 19	ENST00000285599.8	NP_056089.1
MAN2B2	NM_001292038.2	c.134T>G	p.Val45Gly	missense_variant	Exon 1 of 19		NP_001278967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2B2	ENST00000285599.8	c.134T>G	p.Val45Gly	missense_variant	Exon 1 of 19	1	NM_015274.3	ENSP00000285599.3
MAN2B2	ENST00000504248.5	c.134T>G	p.Val45Gly	missense_variant	Exon 1 of 19	2		ENSP00000423129.1
MAN2B2	ENST00000505907.1	c.128T>G	p.Val43Gly	missense_variant	Exon 1 of 17	2		ENSP00000426273.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.7	H;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.38
MutPred		0.83		Loss of stability (P = 0.0047);Loss of stability (P = 0.0047);
MVP		0.48
MPC		0.61
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.95
gMVP		0.61

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: rs890500719; hg19: chr4-6577071;