Variant 5-109690447-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002372.4(MAN2A1):c.30C>A(p.Phe10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MAN2A1
NM_002372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.142

Variant links:

Genes affected

MAN2A1 (HGNC:6824): (mannosidase alpha class 2A member 1) This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus. [provided by RefSeq, Dec 2013]

MAN2A1 links:

MAN2A1-DT (HGNC:):

MAN2A1-DT links:

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ACMG classification

Classification made for transcript

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=0.095618725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2A1	NM_002372.4 linkuse as main transcript	c.30C>A	p.Phe10Leu	missense_variant	1/22	ENST00000261483.5	NP_002363.2	Q16706
MAN2A1	XM_011543395.4 linkuse as main transcript	c.30C>A	p.Phe10Leu	missense_variant	1/17		XP_011541697.1
MAN2A1-DT	NR_186543.1 linkuse as main transcript	n.653G>T		non_coding_transcript_exon_variant	1/1
MAN2A1	XR_007058604.1 linkuse as main transcript	n.521C>A		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN2A1	ENST00000261483.5 linkuse as main transcript	c.30C>A	p.Phe10Leu	missense_variant	1/22	1	NM_002372.4	ENSP00000261483.4		Q16706

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249720

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135238

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.30C>A (p.F10L) alteration is located in exon 1 (coding exon 1) of the MAN2A1 gene. This alteration results from a C to A substitution at nucleotide position 30, causing the phenylalanine (F) at amino acid position 10 to be replaced by a leucine (L). 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.18

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.82

M_CAP

Benign

0.013

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.3

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.94

REVEL

Uncertain

0.33

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.35

MutPred

0.35

Loss of MoRF binding (P = 0.1363);

MVP

0.49

MPC

0.064

ClinPred

0.11

GERP RS

0.49

Varity_R

0.11

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over