1-25753562-G-A

Variant summary

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

The NM_020379.4(MAN1C1):​c.913G>A​(p.Val305Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.884
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.913G>A p.Val305Met missense_variant 5/12 ENST00000374332.9 NP_065112.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAN1C1ENST00000374332.9 linkuse as main transcriptc.913G>A p.Val305Met missense_variant 5/121 NM_020379.4 ENSP00000363452 P1
MAN1C1ENST00000263979.7 linkuse as main transcriptc.373G>A p.Val125Met missense_variant 6/135 ENSP00000263979
MAN1C1ENST00000374329.1 linkuse as main transcriptc.226G>A p.Val76Met missense_variant 4/112 ENSP00000363449
MAN1C1ENST00000473891.1 linkuse as main transcriptn.311G>A non_coding_transcript_exon_variant 4/54

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152234
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250568
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135496
show subpopulations
Gnomad AFR exome
AF:
0.000124
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461272
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
14
AN XY:
726924
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000165
AC:
2

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 GeneticsJan 04, 2022The c.913G>A (p.V305M) alteration is located in exon 5 (coding exon 5) of the MAN1C1 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the valine (V) at amino acid position 305 to be replaced by a methionine (M). 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
0.15
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
21
DANN
Benign
0.88
DEOGEN2
Benign
0.086
.;T;T;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.11
N
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.094
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
.;N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.50
.;N;N;N
REVEL
Benign
0.013
Sift
Benign
0.44
.;T;T;T
Sift4G
Benign
0.34
T;T;T;T
Polyphen
0.39
.;B;.;.
Vest4
0.16
MutPred
0.44
.;Loss of catalytic residue at V305 (P = 0.0666);.;.;
MVP
0.67
MPC
0.57
ClinPred
0.079
T
GERP RS
0.53
Varity_R
0.028
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.29
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.29
Position offset: 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: rs757838115; hg19: chr1-26080053; COSMIC: COSV56047183; API