Genetic Variant MAN1C1:p.Ala147Gly (chr1-25618237-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_020379.4(MAN1C1):c.440C>G(p.Ala147Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,602,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00300

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:

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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=0.080629766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4 link	c.440C>G	p.Ala147Gly	missense_variant	Exon 1 of 12	ENST00000374332.9	NP_065112.1	Q9NR34Q59G34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAN1C1	ENST00000374332.9 link	c.440C>G	p.Ala147Gly	missense_variant	Exon 1 of 12	1	NM_020379.4	ENSP00000363452.4	Q9NR34
MAN1C1	ENST00000263979 link	c.-226C>G		5_prime_UTR_variant	Exon 1 of 13	5		ENSP00000263979.3	B1AJZ5
MAN1C1	ENST00000611903 link	c.-191C>G		5_prime_UTR_variant	Exon 1 of 14				A0A087WZ31

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000453

AC:

AN:

220796

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121360

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:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1449904

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

720324

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.440C>G (p.A147G) alteration is located in exon 1 (coding exon 1) of the MAN1C1 gene. This alteration results from a C to G substitution at nucleotide position 440, causing the alanine (A) at amino acid position 147 to be replaced by a glycine (G). 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

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.011

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

M_CAP

Benign

0.054

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.52

REVEL

Benign

0.18

Sift

Benign

0.47

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.079

MutPred

0.38

Gain of loop (P = 0.0111);

MVP

0.78

MPC

0.51

ClinPred

0.043

GERP RS

2.6

Varity_R

0.042

gMVP

0.26

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