Variant chr12-122129604-A-T 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_014938.6(MLXIP):c.713A>T(p.Asp238Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,400 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MLXIP
NM_014938.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Variant links:

Genes affected

MLXIP (HGNC:17055): (MLX interacting protein) This gene encodes a protein that functions as part of a heterodimer to activate transcription. The encoded protein forms a heterodimer with Max-like protein X (MLX) and is involved in the regulation of genes in response to cellular glucose levels. [provided by RefSeq, Mar 2014]

MLXIP links:

MLXIP (HGNC:):

MLXIP 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=0.22156161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLXIP	NM_014938.6 linkuse as main transcript	c.713A>T	p.Asp238Val	missense_variant	5/17	ENST00000319080.12	NP_055753.3	Q9HAP2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLXIP	ENST00000319080.12 linkuse as main transcript	c.713A>T	p.Asp238Val	missense_variant	5/17	1	NM_014938.6	ENSP00000312834.6		Q9HAP2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248534

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134880

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726954

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

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

May 16, 2024

The c.713A>T (p.D238V) alteration is located in exon 4 (coding exon 4) of the MLXIP gene. This alteration results from a A to T substitution at nucleotide position 713, causing the aspartic acid (D) at amino acid position 238 to be replaced by a valine (V). 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

0.56

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

1.0

M_CAP

Benign

0.041

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.33

Sift

Benign

0.044

Sift4G

Uncertain

0.042

Polyphen

0.76

Vest4

0.39

MutPred

0.26

Loss of solvent accessibility (P = 0.0371);

MVP

0.22

MPC

1.5

ClinPred

0.93

GERP RS

5.0

Varity_R

0.28

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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