Variant 9-70113036-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153267.5(MAMDC2):c.547C>T(p.Arg183Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

MAMDC2
NM_153267.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

MAMDC2 (HGNC:23673): (MAM domain containing 2) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MAMDC2 links:

MAMDC2 (HGNC:):

MAMDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3979682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAMDC2	NM_153267.5 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	5/14	ENST00000377182.5	NP_694999.3
MAMDC2	NM_001347990.2 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	5/12		NP_001334919.1
MAMDC2	NR_125850.1 linkuse as main transcript	n.1164C>T		non_coding_transcript_exon_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAMDC2	ENST00000377182.5 linkuse as main transcript	c.547C>T	p.Arg183Cys	missense_variant	5/14	1	NM_153267.5	ENSP00000366387.4	Q7Z304-1
MAMDC2-AS1	ENST00000414515.7 linkuse as main transcript	n.106+719G>A		intron_variant		5
MAMDC2-AS1	ENST00000591368.5 linkuse as main transcript	n.514+719G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251284

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000189

AC:

276

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000233

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

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

Jul 30, 2024

The c.547C>T (p.R183C) alteration is located in exon 5 (coding exon 5) of the MAMDC2 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 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

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0061

MetaRNN

Benign

0.40

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.23

Sift

Benign

0.041

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.37

MVP

0.60

MPC

0.52

ClinPred

0.50

GERP RS

5.8

Varity_R

0.32

gMVP

0.81

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