Variant 4-2261760-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006454.3(MXD4):c.129G>C(p.Lys43Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MXD4
NM_006454.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.995

Variant links:

Genes affected

MXD4 (HGNC:13906): (MAX dimerization protein 4) This gene is a member of the MAD gene family . The MAD genes encode basic helix-loop-helix-leucine zipper proteins that heterodimerize with MAX protein, forming a transcriptional repression complex. The MAD proteins compete for MAX binding with MYC, which heterodimerizes with MAX forming a transcriptional activation complex. Studies in rodents suggest that the MAD genes are tumor suppressors and contribute to the regulation of cell growth in differentiating tissues. [provided by RefSeq, Jul 2008]

MXD4 links:

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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=0.28775328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXD4	NM_006454.3 link	c.129G>C	p.Lys43Asn	missense_variant	2/6	ENST00000337190.7	NP_006445.1	Q14582

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MXD4	ENST00000337190.7 link	c.129G>C	p.Lys43Asn	missense_variant	2/6	1	NM_006454.3	ENSP00000337889.2	Q14582
MXD4	ENST00000510822.1 link	n.171G>C		non_coding_transcript_exon_variant	2/5	3
MXD4	ENST00000513380.1 link	n.39G>C		non_coding_transcript_exon_variant	1/6	5		ENSP00000422660.1	H0Y8Z5
MXD4	ENST00000515378.5 link	n.171G>C		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1282748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

633792

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 11, 2021

The c.129G>C (p.K43N) alteration is located in exon 2 (coding exon 2) of the MXD4 gene. This alteration results from a G to C substitution at nucleotide position 129, causing the lysine (K) at amino acid position 43 to be replaced by an asparagine (N). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.9

REVEL

Benign

0.077

Sift

Benign

0.058

Sift4G

Uncertain

0.049

Polyphen

0.95

Vest4

0.25

MutPred

0.46

Loss of ubiquitination at K43 (P = 0.0118);

MVP

0.14

MPC

0.66

ClinPred

0.63

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.23

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over