Variant 6-119348750-C-T 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_005907.4(MAN1A1):c.316G>A(p.Glu106Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,408,422 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: 0.0000021 ( 0 hom. )

Consequence

MAN1A1
NM_005907.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Variant links:

Genes affected

MAN1A1 (HGNC:6821): (mannosidase alpha class 1A member 1) This gene encodes a class I mammalian Golgi 1,2-mannosidase which is a type II transmembrane protein. This protein catalyzes the hydrolysis of three terminal mannose residues from peptide-bound Man(9)-GlcNAc(2) oligosaccharides and belongs to family 47 of glycosyl hydrolases. [provided by RefSeq, Jul 2012]

MAN1A1 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=0.15262279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAN1A1	NM_005907.4 linkuse as main transcript	c.316G>A	p.Glu106Lys	missense_variant	2/13	ENST00000368468.4	NP_005898.2
MAN1A1	XM_005266986.5 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant	2/13		XP_005267043.1
MAN1A1	XM_047418775.1 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant	2/6		XP_047274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1A1	ENST00000368468.4 linkuse as main transcript	c.316G>A	p.Glu106Lys	missense_variant	2/13	2	NM_005907.4	ENSP00000357453	P1	P33908-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000522

AC:

AN:

191462

Hom.:

AF XY:

0.00000933

AC XY:

AN XY:

107182

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:

0.0000399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1408422

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

699978

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:

0.0000249

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.19e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 22, 2023

The c.316G>A (p.E106K) alteration is located in exon 2 (coding exon 1) of the MAN1A1 gene. This alteration results from a G to A substitution at nucleotide position 316, causing the glutamic acid (E) at amino acid position 106 to be replaced by a lysine (K). 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

Benign

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Benign

-0.049

Eigen_PC

Benign

0.039

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

M_CAP

Benign

0.066

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.97

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

0.32

Sift4G

Benign

0.25

Polyphen

0.34

Vest4

0.21

MutPred

0.32

Gain of ubiquitination at E106 (P = 0.0039);

MVP

0.24

MPC

0.55

ClinPred

0.31

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.15

gMVP

0.34

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