chr1-25617837-C-T

Variant summary

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

The NM_020379.4(MAN1C1):​c.40C>T​(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MAN1C1
NM_020379.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.201
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16681588).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAN1C1NM_020379.4 linkuse as main transcriptc.40C>T p.Pro14Ser missense_variant 1/12 ENST00000374332.9 NP_065112.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAN1C1ENST00000374332.9 linkuse as main transcriptc.40C>T p.Pro14Ser missense_variant 1/121 NM_020379.4 ENSP00000363452 P1
MAN1C1ENST00000263979.7 linkuse as main transcript upstream_gene_variant 5 ENSP00000263979

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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2023The c.40C>T (p.P14S) alteration is located in exon 1 (coding exon 1) of the MAN1C1 gene. This alteration results from a C to T substitution at nucleotide position 40, causing the proline (P) at amino acid position 14 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
Benign
0.079
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
13
DANN
Benign
0.96
DEOGEN2
Benign
0.0097
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.67
T
M_CAP
Pathogenic
0.89
D
MetaRNN
Benign
0.17
T
MetaSVM
Uncertain
-0.0072
T
MutationAssessor
Benign
0.14
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.49
N
REVEL
Uncertain
0.31
Sift
Benign
0.41
T
Sift4G
Benign
0.18
T
Polyphen
0.0
B
Vest4
0.095
MutPred
0.48
Gain of loop (P = 0.0435);
MVP
0.74
MPC
0.51
ClinPred
0.034
T
GERP RS
-1.5
Varity_R
0.051
gMVP
0.34

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: chr1-25944328; API