Variant chr1-25617963-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020379.4(MAN1C1):c.166C>G(p.Pro56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,608,838 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 75 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.139

Variant links:

Genes affected

MAN1C1 (HGNC:19080): (mannosidase alpha class 1C member 1) Predicted to enable mannosyl-oligosaccharide 1,2-alpha-mannosidase activity. Predicted to be involved in N-glycan processing. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN1C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016571283).

BP6

Variant 1-25617963-C-G is Benign according to our data. Variant chr1-25617963-C-G is described in ClinVar as [Benign]. Clinvar id is 782680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN1C1	NM_020379.4 linkuse as main transcript	c.166C>G	p.Pro56Ala	missense_variant	1/12	ENST00000374332.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1C1	ENST00000374332.9 linkuse as main transcript	c.166C>G	p.Pro56Ala	missense_variant	1/12	1	NM_020379.4	P1
MAN1C1	ENST00000263979.7 linkuse as main transcript	c.-500C>G		5_prime_UTR_variant	1/13	5

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

2564

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00693

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:

0.000147

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00415

AC:

997

AN:

240378

Hom.:

AF XY:

0.00317

AC XY:

417

AN XY:

131566

show subpopulations

Gnomad AFR exome

AF:

0.0601

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000997

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000840

Gnomad OTH exome

AF:

0.00188

GnomAD4 exome

AF:

0.00169

AC:

2467

AN:

1456516

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1069

AN XY:

724618

show subpopulations

Gnomad4 AFR exome

AF:

0.0598

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000685

Gnomad4 OTH exome

AF:

0.00412

GnomAD4 genome

AF:

0.0169

AC:

2567

AN:

152322

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1221

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0585

Gnomad4 AMR

AF:

0.00692

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.000954

Hom.:

Bravo

AF:

0.0194

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0538

AC:

236

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00506

AC:

613

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.61

REVEL

Benign

0.071

Sift

Uncertain

0.016

Sift4G

Benign

0.47

Polyphen

0.0030

Vest4

0.17

MVP

0.74

MPC

0.50

ClinPred

0.0014

GERP RS

1.5

Varity_R

0.041

gMVP

0.32

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