chr1-117368332-G-A

Position:

• chr1-117368332-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006699.5(MAN1A2):​c.149G>A​(p.Cys50Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: MAN1A2 NM_006699.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

Genes affected

MAN1A2 (HGNC:6822): (mannosidase alpha class 1A member 2) Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. See MAN2A1 (MIM 154582) for general information.[supplied by OMIM, Mar 2008]

MAN1A2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1A2	NM_006699.5	c.149G>A	p.Cys50Tyr	missense_variant	1/13	ENST00000356554.7	NP_006690.1
MAN1A2	XM_006710302.4	c.149G>A	p.Cys50Tyr	missense_variant	1/14		XP_006710365.1
MAN1A2	XM_011540536.4	c.149G>A	p.Cys50Tyr	missense_variant	1/13		XP_011538838.1
MAN1A2	XM_017000115.2	c.149G>A	p.Cys50Tyr	missense_variant	1/7		XP_016855604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1A2	ENST00000356554.7	c.149G>A	p.Cys50Tyr	missense_variant	1/13	1	NM_006699.5	ENSP00000348959.3
MAN1A2	ENST00000482811.1	n.390G>A		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2024

The c.149G>A (p.C50Y) alteration is located in exon 1 (coding exon 1) of the MAN1A2 gene. This alteration results from a G to A substitution at nucleotide position 149, causing the cysteine (C) at amino acid position 50 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.0	L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.8	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.74		Loss of stability (P = 0.1595);
MVP		0.45
MPC		2.1
ClinPred		1.0	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.59
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-117910954;