chr15-75356198-G-A

Position:

chr15-75356198-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006715.4(MAN2C1):c.2908C>T(p.Arg970Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.000024 ( 0 hom. )

Consequence

MAN2C1
NM_006715.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.900

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14548367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2C1	NM_006715.4 linkuse as main transcript	c.2908C>T	p.Arg970Cys	missense_variant	25/26	ENST00000267978.10	NP_006706.2	Q9NTJ4-1A0A140VJN9
NEIL1	NM_024608.4 linkuse as main transcript	c.*1164G>A		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.2908C>T	p.Arg970Cys	missense_variant	25/26	1	NM_006715.4	ENSP00000267978.4		Q9NTJ4-1
NEIL1	ENST00000355059.9 linkuse as main transcript	c.*1164G>A		3_prime_UTR_variant	10/10	2	NM_024608.4	ENSP00000347170.4		Q96FI4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000403

AC:

AN:

248262

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134896

show subpopulations

Gnomad AFR exome

AF:

0.0000639

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000626

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1460992

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000495

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.2908C>T (p.R970C) alteration is located in exon 25 (coding exon 25) of the MAN2C1 gene. This alteration results from a C to T substitution at nucleotide position 2908, causing the arginine (R) at amino acid position 970 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.62

.;.;.;D;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;.;L;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;N;N;N;.

REVEL

Benign

0.037

Sift

Benign

0.032

D;D;D;D;.

Sift4G

Uncertain

0.023

D;D;D;D;D

Polyphen

0.013

.;.;.;B;.

Vest4

0.34

MutPred

0.59

.;.;.;Loss of disorder (P = 0.0149);.;

MVP

0.18

MPC

0.11

ClinPred

0.066

GERP RS

0.064

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.090

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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