1-25686470-C-T

Variant summary

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

The NM_020379.4(MAN1C1):​c.571C>T​(p.Arg191Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000874 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

13
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAN1C1NM_020379.4 linkuse as main transcriptc.571C>T p.Arg191Cys 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.571C>T p.Arg191Cys missense_variant 2/121 NM_020379.4 ENSP00000363452 P1
MAN1C1ENST00000263979.7 linkuse as main transcriptc.31C>T p.Arg11Cys missense_variant 3/135 ENSP00000263979
MAN1C1ENST00000473891.1 linkuse as main transcript upstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251492
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135920
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000903
AC:
132
AN:
1461840
Hom.:
0
Cov.:
30
AF XY:
0.000106
AC XY:
77
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000112
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000158
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000164
EpiControl
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 20, 2023The c.571C>T (p.R191C) alteration is located in exon 2 (coding exon 2) of the MAN1C1 gene. This alteration results from a C to T substitution at nucleotide position 571, causing the arginine (R) at amino acid position 191 to be replaced by a cysteine (C). 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
0.11
BayesDel_addAF
Benign
-0.074
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D;D
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Uncertain
-0.020
T
MutationAssessor
Uncertain
2.9
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-4.2
D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.015
D;D
Sift4G
Benign
0.071
T;D
Polyphen
0.95
P;.
Vest4
0.53
MVP
0.84
MPC
1.2
ClinPred
0.94
D
GERP RS
5.2
Varity_R
0.19
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs375175751; hg19: chr1-26012961; COSMIC: COSV99847966; COSMIC: COSV99847966; API