12-122138270-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014938.6(MLXIP):c.2231G>A(p.Ser744Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MLXIP NM_014938.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLXIP	NM_014938.6	c.2231G>A	p.Ser744Asn	missense_variant	13/17	ENST00000319080.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLXIP	ENST00000319080.12	c.2231G>A	p.Ser744Asn	missense_variant	13/17	1	NM_014938.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.2231G>A (p.S744N) alteration is located in exon 12 (coding exon 12) of the MLXIP gene. This alteration results from a G to A substitution at nucleotide position 2231, causing the serine (S) at amino acid position 744 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	Benign	0.089
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.39	T;.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Pathogenic	1.1	D
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.32
MutPred		0.39		Gain of catalytic residue at S747 (P = 5e-04);.;.;
MVP		0.34
MPC		1.0
ClinPred		0.96	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.22

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.

Other links and lift over

hg19: chr12-122622817;