NM_014938.6:c.1858C>T

Variant names:

• chr12-122135492-C-T
• rs1414966423
• NM_014938.6:c.1858C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014938.6(MLXIP):​c.1858C>T​(p.Pro620Ser) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLXIP NM_014938.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57
• Publications: 0 publications found

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

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=0.11764094).

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.1858C>T	p.Pro620Ser	missense	Exon 11 of 17	NP_055753.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLXIP	ENST00000319080.12	TSL:1 MANE Select	c.1858C>T	p.Pro620Ser	missense	Exon 11 of 17	ENSP00000312834.6	Q9HAP2-1
	MLXIP	ENST00000538698.5	TSL:1	c.679C>T	p.Pro227Ser	missense	Exon 3 of 9	ENSP00000440769.1	Q9HAP2-2
	MLXIP	ENST00000890512.1		c.1858C>T	p.Pro620Ser	missense	Exon 11 of 17	ENSP00000560571.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.028
Sift	Benign	0.41	T
Sift4G	Benign	0.091	T
Polyphen		0.0040	B
Vest4		0.26
MutPred		0.38		Gain of catalytic residue at V622 (P = 0.0012)
MVP		0.20
MPC		0.45
ClinPred		0.54	D
GERP RS		3.7
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.40
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1414966423; hg19: chr12-122620039;