Genetic Variant MAN1C1:p.Ala173Thr (chr1-25618314-G-A) – 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.517G>A(p.Ala173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000345 in 1,449,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.829

Publications

0 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=0.09110215).

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.517G>A	p.Ala173Thr	missense	Exon 1 of 12	NP_065112.1	Q9NR34
MAN1C1	NM_001385182.1		c.517G>A	p.Ala173Thr	missense	Exon 1 of 13	NP_001372111.1
MAN1C1	NM_001385183.1		c.517G>A	p.Ala173Thr	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.517G>A	p.Ala173Thr	missense	Exon 1 of 12	ENSP00000363452.4	Q9NR34
MAN1C1	ENST00000899084.1		c.517G>A	p.Ala173Thr	missense	Exon 1 of 12	ENSP00000569143.1
MAN1C1	ENST00000929760.1		c.517G>A	p.Ala173Thr	missense	Exon 1 of 11	ENSP00000599819.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000903

AC:

AN:

221444

AF XY:

0.00000825

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:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000345

AC:

AN:

1449768

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

720142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33084

American (AMR)

AF:

0.00

AC:

AN:

42548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25762

East Asian (EAS)

AF:

0.00

AC:

AN:

39042

South Asian (SAS)

AF:

0.00

AC:

AN:

83740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000424

AC:

AN:

1108256

Other (OTH)

AF:

0.0000499

AC:

AN:

60096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.29

M_CAP

Benign

0.055

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.81

PhyloP100

0.83

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.73

REVEL

Benign

0.22

Sift

Benign

0.19

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.044

MutPred

0.55

Gain of loop (P = 0.0166)

MVP

0.74

MPC

0.49

ClinPred

0.085

GERP RS

3.2

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.082

gMVP

0.23

Mutation Taster

=81/19

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