1-25686490-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020379.4(MAN1C1):​c.591C>A​(p.Asn197Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAN1C1NM_020379.4 linkuse as main transcriptc.591C>A p.Asn197Lys missense_variant 2/12 ENST00000374332.9 NP_065112.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAN1C1ENST00000374332.9 linkuse as main transcriptc.591C>A p.Asn197Lys missense_variant 2/121 NM_020379.4 ENSP00000363452 P1
MAN1C1ENST00000263979.7 linkuse as main transcriptc.51C>A p.Asn17Lys missense_variant 3/135 ENSP00000263979
MAN1C1ENST00000473891.1 linkuse as main transcript upstream_gene_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251490
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461884
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000328
Hom.:
0

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 submitterclinical testingAmbry GeneticsApr 01, 2024The c.591C>A (p.N197K) alteration is located in exon 2 (coding exon 2) of the MAN1C1 gene. This alteration results from a C to A substitution at nucleotide position 591, causing the asparagine (N) at amino acid position 197 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
Pathogenic
0.99
BayesDel_addAF
Benign
0.0091
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
13
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
D;D
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.087
N
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.28
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Pathogenic
3.2
M;.
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-5.5
D;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;.
Vest4
0.95
MutPred
0.69
Gain of methylation at N197 (P = 0.0073);.;
MVP
0.83
MPC
1.5
ClinPred
1.0
D
GERP RS
-4.9
Varity_R
0.81
gMVP
0.93

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.

Other links and lift over

dbSNP: rs368461290; hg19: chr1-26012981; API