Variant 6-119290706-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005907.4(MAN1A1):c.874G>A(p.Ala292Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,610,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

MAN1A1
NM_005907.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1A1	NM_005907.4 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	5/13	ENST00000368468.4	NP_005898.2	P33908-1
MAN1A1	XM_005266986.5 linkuse as main transcript	c.1123G>A	p.Ala375Thr	missense_variant	5/13		XP_005267043.1
MAN1A1	XM_011535833.3 linkuse as main transcript	c.307G>A	p.Ala103Thr	missense_variant	4/12		XP_011534135.1
MAN1A1	XM_047418775.1 linkuse as main transcript	c.1123G>A	p.Ala375Thr	missense_variant	5/6		XP_047274731.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1A1	ENST00000368468.4 linkuse as main transcript	c.874G>A	p.Ala292Thr	missense_variant	5/13	2	NM_005907.4	ENSP00000357453.3		P33908-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000946

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000265

AC:

AN:

249040

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

229

AN:

1458874

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

725758

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.000171

AC:

AN:

151926

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000946

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000274

EpiControl

AF:

0.000297

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

Feb 10, 2022

The c.874G>A (p.A292T) alteration is located in exon 5 (coding exon 4) of the MAN1A1 gene. This alteration results from a G to A substitution at nucleotide position 874, causing the alanine (A) at amino acid position 292 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.70

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.45

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.043

Polyphen

1.0

Vest4

0.95

MVP

0.85

MPC

1.3

ClinPred

0.37

GERP RS

5.9

Varity_R

0.36

gMVP

0.91

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