Variant chr1-117402200-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006699.5(MAN1A2):c.317G>A(p.Arg106His) variant causes a missense change. The variant allele was found at a frequency of 0.000824 in 1,609,952 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R106C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 2 hom. )

Consequence

MAN1A2
NM_006699.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036024332).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAN1A2	NM_006699.5 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	2/13	ENST00000356554.7
MAN1A2	XM_006710302.4 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	2/14
MAN1A2	XM_011540536.4 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	2/13
MAN1A2	XM_017000115.2 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1A2	ENST00000356554.7 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	2/13	1	NM_006699.5	P1
MAN1A2	ENST00000482811.1 linkuse as main transcript	n.544-12513G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000432

AC:

107

AN:

247560

Hom.:

AF XY:

0.000462

AC XY:

AN XY:

134090

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.000264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000673

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.000792

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000861

AC:

1255

AN:

1457714

Hom.:

Cov.:

AF XY:

0.000854

AC XY:

619

AN XY:

724976

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.000399

GnomAD4 genome

AF:

0.000473

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000412

AC:

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

Jul 09, 2021

The c.317G>A (p.R106H) alteration is located in exon 2 (coding exon 2) of the MAN1A2 gene. This alteration results from a G to A substitution at nucleotide position 317, causing the arginine (R) at amino acid position 106 to be replaced by a histidine (H). 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

0.096

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

M_CAP

Benign

0.058

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.87

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.68

REVEL

Benign

0.24

Sift

Benign

0.19

Sift4G

Benign

0.17

Polyphen

0.63

Vest4

0.31

MVP

0.64

MPC

1.0

ClinPred

0.043

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.35

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