Genetic Variant MLXIP:p.Gly66Ser (chr12-122079049-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014938.6(MLXIP):c.196G>A(p.Gly66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 1,344,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MLXIP
NM_014938.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.952

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08279106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014938.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLXIP	NM_014938.6	MANE Select	c.196G>A	p.Gly66Ser	missense	Exon 1 of 17	NP_055753.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLXIP	ENST00000319080.12	TSL:1 MANE Select	c.196G>A	p.Gly66Ser	missense	Exon 1 of 17	ENSP00000312834.6	Q9HAP2-1
MLXIP	ENST00000890512.1		c.196G>A	p.Gly66Ser	missense	Exon 1 of 17	ENSP00000560571.1
MLXIP	ENST00000890511.1		c.196G>A	p.Gly66Ser	missense	Exon 1 of 17	ENSP00000560570.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000894

AC:

AN:

111870

AF XY:

0.0000161

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000508

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000223

AC:

AN:

1344582

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

AN XY:

663122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28146

American (AMR)

AF:

0.0000642

AC:

AN:

31158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23812

East Asian (EAS)

AF:

0.00

AC:

AN:

30408

South Asian (SAS)

AF:

0.0000133

AC:

AN:

75388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1056758

Other (OTH)

AF:

0.00

AC:

AN:

55598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.39

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

PhyloP100

0.95

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.43

REVEL

Benign

0.015

Sift

Pathogenic

0.0

Sift4G

Benign

0.33

Polyphen

0.020

Vest4

0.086

MutPred

0.26

Gain of catalytic residue at P70 (P = 2e-04)

MVP

0.093

MPC

1.2

ClinPred

0.98

GERP RS

2.7

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.14

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over