dbSNP rs781600564: MAN1C1:p.Pro14Ala (chr1-25617837-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020379.4(MAN1C1):c.40C>G(p.Pro14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Publications

1 publications found

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]

MAN1C1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17927563).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAN1C1	NM_020379.4	MANE Select	c.40C>G	p.Pro14Ala	missense	Exon 1 of 12	NP_065112.1	Q9NR34
MAN1C1	NM_001385182.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 13	NP_001372111.1
MAN1C1	NM_001385183.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 12	NP_001372112.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAN1C1	ENST00000374332.9	TSL:1 MANE Select	c.40C>G	p.Pro14Ala	missense	Exon 1 of 12	ENSP00000363452.4	Q9NR34
MAN1C1	ENST00000899084.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 12	ENSP00000569143.1
MAN1C1	ENST00000929760.1		c.40C>G	p.Pro14Ala	missense	Exon 1 of 11	ENSP00000599819.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000424

AC:

AN:

235612

AF XY:

0.00000774

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453604

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32576

American (AMR)

AF:

0.00

AC:

AN:

44044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25920

East Asian (EAS)

AF:

0.00

AC:

AN:

38888

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109128

Other (OTH)

AF:

0.00

AC:

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.9

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.010

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.18

MetaSVM

Uncertain

-0.0044

MutationAssessor

Benign

1.2

PhyloP100

-0.20

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.63

REVEL

Uncertain

0.32

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.11

MutPred

0.52

Gain of catalytic residue at P14 (P = 0.0047)

MVP

0.70

MPC

0.49

ClinPred

0.032

GERP RS

-1.5

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.049

gMVP

0.32

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over