chr12-122079025-C-T

Variant names:

• chr12-122079025-C-T
• NM_014938.6:c.172C>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.172C>T​(p.Pro58Ser) 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. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MLXIP NM_014938.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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=0.2002284).

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.172C>T	p.Pro58Ser	missense	Exon 1 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.172C>T	p.Pro58Ser	missense	Exon 1 of 17	ENSP00000312834.6	Q9HAP2-1
	MLXIP	ENST00000890512.1		c.172C>T	p.Pro58Ser	missense	Exon 1 of 17	ENSP00000560571.1
	MLXIP	ENST00000890511.1		c.172C>T	p.Pro58Ser	missense	Exon 1 of 17	ENSP00000560570.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1196864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 587596

African (AFR) AF: 0.00 AC: 0 AN: 22344

American (AMR) AF: 0.00 AC: 0 AN: 10864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17932

East Asian (EAS) AF: 0.00 AC: 0 AN: 23678

South Asian (SAS) AF: 0.00 AC: 0 AN: 58518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 982170

Other (OTH) AF: 0.00 AC: 0 AN: 47180

GnomAD4 genome Cov.: 31

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	0.078
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.57	D
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.059
Sift	Uncertain	0.027	D
Sift4G	Benign	0.84	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.22		Gain of catalytic residue at P60 (P = 5e-04)
MVP		0.13
MPC		0.43
ClinPred		0.71	D
GERP RS		2.8
PromoterAI		0.30	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.28
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr12-122516931;