Genetic Variant MAN1C1:c.1047+198G>T (chr1-25758907-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020379.4(MAN1C1):c.1047+198G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 584,942 control chromosomes in the GnomAD database, including 1,667 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.079 ( 538 hom., cov: 32)

Exomes 𝑓: 0.064 ( 1129 hom. )

Consequence

MAN1C1
NM_020379.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
MAN1C1	NM_020379.4	MANE Select	c.1047+198G>T	intron	N/A	NP_065112.1	Q9NR34
MAN1C1	NM_001385182.1		c.1149+198G>T	intron	N/A	NP_001372111.1
MAN1C1	NM_001385183.1		c.1119+126G>T	intron	N/A	NP_001372112.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAN1C1	ENST00000374332.9	TSL:1 MANE Select	c.1047+198G>T	intron	N/A	ENSP00000363452.4	Q9NR34
MAN1C1	ENST00000899084.1		c.1119+126G>T	intron	N/A	ENSP00000569143.1
MAN1C1	ENST00000929760.1		c.966+198G>T	intron	N/A	ENSP00000599819.1

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

12012

AN:

151934

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0784

GnomAD4 exome

AF:

0.0642

AC:

27811

AN:

432890

Hom.:

1129

Cov.:

AF XY:

0.0613

AC XY:

14050

AN XY:

229226

show subpopulations

African (AFR)

AF:

0.116

AC:

1405

AN:

12164

American (AMR)

AF:

0.0389

AC:

732

AN:

18822

Ashkenazi Jewish (ASJ)

AF:

0.0800

AC:

1046

AN:

13070

East Asian (EAS)

AF:

0.0000679

AC:

AN:

29476

South Asian (SAS)

AF:

0.0207

AC:

955

AN:

46190

European-Finnish (FIN)

AF:

0.0651

AC:

1807

AN:

27740

Middle Eastern (MID)

AF:

0.0666

AC:

205

AN:

3076

European-Non Finnish (NFE)

AF:

0.0774

AC:

19937

AN:

257418

Other (OTH)

AF:

0.0691

AC:

1722

AN:

24934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1194

2387

3581

4774

5968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.0791

AC:

12020

AN:

152052

Hom.:

538

Cov.:

AF XY:

0.0751

AC XY:

5585

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.111

AC:

4595

AN:

41510

American (AMR)

AF:

0.0526

AC:

804

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0888

AC:

308

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0147

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0607

AC:

644

AN:

10614

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0787

AC:

5338

AN:

67828

Other (OTH)

AF:

0.0776

AC:

164

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

584

1169

1753

2338

2922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0205

Hom.:

Bravo

AF:

0.0800

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.55

(source)

DANN

Benign

0.55

PhyloP100

-0.032

Mutation Taster

=100/0

polymorphism (auto)

(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

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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