15-75356838-C-G

Position:

chr15-75356838-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_006715.4(MAN2C1):c.2612G>C(p.Cys871Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,614,004 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 2 hom. )

Consequence

MAN2C1
NM_006715.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.10

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:

MAN2C1 (HGNC:):

MAN2C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 15-75356838-C-G is Pathogenic according to our data. Variant chr15-75356838-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1342928.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-75356838-C-G is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.12653661). . Strength limited to SUPPORTING due to the PP5.

BS2

High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2C1	NM_006715.4 linkuse as main transcript	c.2612G>C	p.Cys871Ser	missense_variant	22/26	ENST00000267978.10	NP_006706.2	Q9NTJ4-1A0A140VJN9
NEIL1	NM_024608.4 linkuse as main transcript	c.*1804C>G		3_prime_UTR_variant	10/10	ENST00000355059.9	NP_078884.2	Q96FI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN2C1	ENST00000267978.10 linkuse as main transcript	c.2612G>C	p.Cys871Ser	missense_variant	22/26	1	NM_006715.4	ENSP00000267978.4		Q9NTJ4-1
NEIL1	ENST00000355059.9 linkuse as main transcript	c.*1804C>G		3_prime_UTR_variant	10/10	2	NM_024608.4	ENSP00000347170.4		Q96FI4

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000473

AC:

119

AN:

251328

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000959

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000907

AC:

1326

AN:

1461762

Hom.:

Cov.:

AF XY:

0.000866

AC XY:

630

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000440

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000820

Hom.:

Bravo

AF:

0.000416

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000771

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Congenital disorder of deglycosylation 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Uncertain

0.61

.;.;.;D;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

T;T;T;T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.54

N;.;.;N;.

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.5

D;D;D;D;.

REVEL

Benign

0.24

Sift

Benign

0.44

T;T;T;T;.

Sift4G

Benign

0.82

T;T;T;T;T

Polyphen

0.024

.;.;.;B;.

Vest4

0.40

MutPred

0.77

Gain of disorder (P = 0.0066);.;.;Gain of disorder (P = 0.0066);.;

MVP

0.79

MPC

0.11

ClinPred

0.065

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over