Variant 2-69935388-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002357.4(MXD1):c.241G>C(p.Gly81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,850 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MXD1
NM_002357.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

MXD1 (HGNC:6761): (MAX dimerization protein 1) This gene encodes a member of the MYC/MAX/MAD network of basic helix-loop-helix leucine zipper transcription factors. The MYC/MAX/MAD transcription factors mediate cellular proliferation, differentiation and apoptosis. The encoded protein antagonizes MYC-mediated transcriptional activation of target genes by competing for the binding partner MAX and recruiting repressor complexes containing histone deacetylases. Mutations in this gene may play a role in acute leukemia, and the encoded protein is a potential tumor suppressor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

MXD1 links:

ASPRV1 (HGNC:):

ASPRV1 links:

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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=0.15799344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MXD1	NM_002357.4 linkuse as main transcript	c.241G>C	p.Gly81Arg	missense_variant	4/6	ENST00000264444.7	NP_002348.1	Q05195-1
MXD1	NM_001202513.2 linkuse as main transcript	c.241G>C	p.Gly81Arg	missense_variant	4/6		NP_001189442.1	Q05195B7ZLI7
MXD1	NM_001202514.2 linkuse as main transcript	c.211G>C	p.Gly71Arg	missense_variant	3/5		NP_001189443.1	Q05195-2
ASPRV1	NR_170375.1 linkuse as main transcript	n.1101-2195C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MXD1	ENST00000264444.7 linkuse as main transcript	c.241G>C	p.Gly81Arg	missense_variant	4/6	1	NM_002357.4	ENSP00000264444.2	Q05195-1
MXD1	ENST00000540449.5 linkuse as main transcript	c.211G>C	p.Gly71Arg	missense_variant	3/5	1		ENSP00000443935.1	Q05195-2
MXD1	ENST00000435990.5 linkuse as main transcript	c.145G>C	p.Gly49Arg	missense_variant	6/8	3		ENSP00000410672.1	C9JBE8
MXD1	ENST00000409442.2 linkuse as main transcript	n.115G>C		non_coding_transcript_exon_variant	3/5	2		ENSP00000386523.2	F8WBI0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251484

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Feb 22, 2023

The c.241G>C (p.G81R) alteration is located in exon 4 (coding exon 4) of the MXD1 gene. This alteration results from a G to C substitution at nucleotide position 241, causing the glycine (G) at amino acid position 81 to be replaced by an arginine (R). 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

0.33

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

.;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

-1.1

.;.;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.33

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.34

.;.;B

Vest4

0.48, 0.44

MutPred

0.31

.;.;Gain of solvent accessibility (P = 0.0097);

MVP

0.97

MPC

0.99

ClinPred

0.38

GERP RS

5.9

Varity_R

0.13

gMVP

0.26

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