Genetic Variant MAN2C1:p.Val950Met (chr15-75356339-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_006715.4(MAN2C1):c.2848G>A(p.Val950Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,612,492 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

MAN2C1
NM_006715.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0440

Publications

3 publications found

Variant links:

Genes affected

MAN2C1 (HGNC:6827): (mannosidase alpha class 2C member 1) Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAN2C1 links:

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

NEIL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26487878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAN2C1	NM_006715.4	MANE Select	c.2848G>A	p.Val950Met	missense	Exon 24 of 26	NP_006706.2
NEIL1	NM_024608.4	MANE Select	c.*1305C>T		3_prime_UTR	Exon 10 of 10	NP_078884.2	Q96FI4
MAN2C1	NM_001256494.2		c.2899G>A	p.Val967Met	missense	Exon 24 of 26	NP_001243423.1	Q9NTJ4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAN2C1	ENST00000267978.10	TSL:1 MANE Select	c.2848G>A	p.Val950Met	missense	Exon 24 of 26	ENSP00000267978.4	Q9NTJ4-1
MAN2C1	ENST00000565683.5	TSL:1	c.2899G>A	p.Val967Met	missense	Exon 24 of 26	ENSP00000457788.1	Q9NTJ4-4
MAN2C1	ENST00000569482.5	TSL:1	c.2779G>A	p.Val927Met	missense	Exon 24 of 26	ENSP00000455998.1	Q9NTJ4-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151984

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:

0.000772

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000771

AC:

AN:

246502

AF XY:

0.0000747

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.000549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1460390

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

726370

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33458

American (AMR)

AF:

0.0000225

AC:

AN:

44458

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26088

East Asian (EAS)

AF:

0.00106

AC:

AN:

39668

South Asian (SAS)

AF:

0.000105

AC:

AN:

86018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53086

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111518

Other (OTH)

AF:

0.0000829

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0000329

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41504

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000774

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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:

0.0000770

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000577

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

0.25

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

Eigen

Benign

-0.74

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.26

MetaSVM

Uncertain

0.060

MutationAssessor

Uncertain

2.8

PhyloP100

0.044

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.36

Sift

Uncertain

0.024

Sift4G

Uncertain

0.036

Polyphen

0.88

Vest4

0.38

MutPred

0.23

Loss of sheet (P = 0.0084)

MVP

0.63

MPC

0.29

ClinPred

0.15

GERP RS

-4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.45

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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