Genetic Variant MAN1C1:p.Arg103Cys (chr1-25618104-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020379.4(MAN1C1):c.307C>T(p.Arg103Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,513,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061229587).

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.307C>T	p.Arg103Cys	missense	Exon 1 of 12	NP_065112.1	Q9NR34
MAN1C1	NM_001385182.1		c.307C>T	p.Arg103Cys	missense	Exon 1 of 13	NP_001372111.1
MAN1C1	NM_001385183.1		c.307C>T	p.Arg103Cys	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.307C>T	p.Arg103Cys	missense	Exon 1 of 12	ENSP00000363452.4	Q9NR34
MAN1C1	ENST00000263979.7	TSL:5	c.-359C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000263979.3	B1AJZ5
MAN1C1	ENST00000899084.1		c.307C>T	p.Arg103Cys	missense	Exon 1 of 12	ENSP00000569143.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000151

AC:

AN:

105816

AF XY:

0.000234

show subpopulations

Gnomad AFR exome

AF:

0.000365

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:

0.0000231

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1361278

Hom.:

Cov.:

AF XY:

0.0000461

AC XY:

AN XY:

671822

show subpopulations

African (AFR)

AF:

0.0000355

AC:

AN:

28132

American (AMR)

AF:

0.00

AC:

AN:

29732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23852

East Asian (EAS)

AF:

0.00

AC:

AN:

33424

South Asian (SAS)

AF:

0.000328

AC:

AN:

76178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4964

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

1070894

Other (OTH)

AF:

0.0000706

AC:

AN:

56688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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

AF:

0.0000131

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000873

AC:

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

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.2

PhyloP100

4.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.29

Sift

Uncertain

0.023

Sift4G

Uncertain

0.032

Polyphen

0.82

Vest4

0.21

MutPred

0.43

Loss of solvent accessibility (P = 0.0079)

MVP

0.82

MPC

1.0

ClinPred

0.30

GERP RS

3.1

PromoterAI

0.0044

Neutral

(source)

Varity_R

0.14

gMVP

0.44

Mutation Taster

=83/17

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over