1-25617939-C-A

Variant summary

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

The NM_020379.4(MAN1C1):​c.142C>A​(p.Arg48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R48L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MAN1C1
NM_020379.4 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65
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]

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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 rank MANE Protein UniProt
MAN1C1NM_020379.4 linkc.142C>A p.Arg48Ser missense_variant Exon 1 of 12 ENST00000374332.9 NP_065112.1 Q9NR34Q59G34

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAN1C1ENST00000374332.9 linkc.142C>A p.Arg48Ser missense_variant Exon 1 of 12 1 NM_020379.4 ENSP00000363452.4 Q9NR34
MAN1C1ENST00000263979 linkc.-524C>A 5_prime_UTR_variant Exon 1 of 13 5 ENSP00000263979.3 B1AJZ5
MAN1C1ENST00000611903 linkc.-489C>A 5_prime_UTR_variant Exon 1 of 14 A0A087WZ31

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.142C>A (p.R48S) alteration is located in exon 1 (coding exon 1) of the MAN1C1 gene. This alteration results from a C to A substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a serine (S). 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
Uncertain
0.47
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T
Eigen
Benign
0.15
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.93
D
M_CAP
Pathogenic
0.94
D
MetaRNN
Uncertain
0.43
T
MetaSVM
Uncertain
0.69
D
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.59
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.15
T
Polyphen
0.92
P
Vest4
0.26
MutPred
0.65
Gain of helix (P = 0.0164);
MVP
0.92
MPC
1.3
ClinPred
0.80
D
GERP RS
4.0
Varity_R
0.24
gMVP
0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-25944430; API