rs1170877618

Variant names:

• chr12-122079049-G-A
• rs1170877618
• NM_014938.6:c.196G>A

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.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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.952
• 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=0.08279106).

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

Sel.	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.: 31

GnomAD2 exomes AF: 0.00000894 AC: 1 AN: 111870 AF XY: 0.0000161

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: 3 AN: 1344582 Hom.: 0 Cov.: 31 AF XY: 0.00000302 AC XY: 2 AN XY: 663122

African (AFR) AF: 0.00 AC: 0 AN: 28146

American (AMR) AF: 0.0000642 AC: 2 AN: 31158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23812

East Asian (EAS) AF: 0.00 AC: 0 AN: 30408

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056758

Other (OTH) AF: 0.00 AC: 0 AN: 55598

GnomAD4 genome Cov.: 31

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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.39	N
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.95
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.33	T
Polyphen		0.020	B
Vest4		0.086
MutPred		0.26		Gain of catalytic residue at P70 (P = 2e-04)
MVP		0.093
MPC		1.2
ClinPred		0.98	D
GERP RS		2.7
PromoterAI		-0.039	Neutral
Varity_R		0.14
gMVP		0.15
Mutation Taster		=99/1	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

dbSNP: rs1170877618; hg19: chr12-122516955;