4-6575256-C-G

Variant names:

• chr4-6575256-C-G
• rs1226757941
• NM_015274.3:c.46C>G

Variant summary

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

The NM_015274.3(MAN2B2):​c.46C>G​(p.Leu16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MAN2B2 NM_015274.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07056168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2B2	NM_015274.3	c.46C>G	p.Leu16Val	missense_variant	Exon 1 of 19	ENST00000285599.8	NP_056089.1
MAN2B2	NM_001292038.2	c.46C>G	p.Leu16Val	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.46C>G	p.Leu16Val	missense_variant	Exon 1 of 19	1	NM_015274.3	ENSP00000285599.3
MAN2B2	ENST00000504248.5	c.46C>G	p.Leu16Val	missense_variant	Exon 1 of 19	2		ENSP00000423129.1
MAN2B2	ENST00000505907.1	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 17	2		ENSP00000426273.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395366 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000273

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.8
DANN	Benign	0.46
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.25
Sift	Benign	0.057	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.049	B;B
Vest4		0.23
MutPred		0.48		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);
MVP		0.48
MPC		0.13
ClinPred		0.082	T
GERP RS		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.072
gMVP		0.31

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: rs1226757941; hg19: chr4-6576983;