Variant rs3812316 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032951.3(MLXIPL):c.723G>C(p.Gln241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,585,936 control chromosomes in the GnomAD database, including 11,463 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.095 ( 810 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10653 hom. )

Consequence

MLXIPL
NM_032951.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

MLXIPL (HGNC:12744): (MLX interacting protein like) This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MLXIPL links:

MLXIPL (HGNC:):

MLXIPL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015729964).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLXIPL	NM_032951.3 linkuse as main transcript	c.723G>C	p.Gln241His	missense_variant	6/17	ENST00000313375.8	NP_116569.1	Q9NP71-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLXIPL	ENST00000313375.8 linkuse as main transcript	c.723G>C	p.Gln241His	missense_variant	6/17	1	NM_032951.3	ENSP00000320886.3		Q9NP71-1

Frequencies

GnomAD3 genomes

AF:

0.0946

AC:

14400

AN:

152206

Hom.:

809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0711

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.0925

Gnomad SAS

AF:

0.0879

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.0869

GnomAD3 exomes

AF:

0.101

AC:

20140

AN:

200060

Hom.:

1113

AF XY:

0.102

AC XY:

10988

AN XY:

107430

show subpopulations

Gnomad AFR exome

AF:

0.0418

Gnomad AMR exome

AF:

0.0621

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0863

Gnomad SAS exome

AF:

0.0903

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.119

AC:

169931

AN:

1433610

Hom.:

10653

Cov.:

AF XY:

0.118

AC XY:

83866

AN XY:

710372

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.0615

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.0914

Gnomad4 SAS exome

AF:

0.0906

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0946

AC:

14408

AN:

152326

Hom.:

810

Cov.:

AF XY:

0.0942

AC XY:

7017

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0436

Gnomad4 AMR

AF:

0.0709

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.0929

Gnomad4 SAS

AF:

0.0882

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.0912

Alfa

AF:

0.118

Hom.:

849

Bravo

AF:

0.0863

TwinsUK

AF:

0.123

AC:

455

ALSPAC

AF:

0.135

AC:

521

ESP6500AA

AF:

0.0447

AC:

197

ESP6500EA

AF:

0.119

AC:

1027

ExAC

AF:

0.0863

AC:

10397

Asia WGS

AF:

0.102

AC:

353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.097

.;.;T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.63

T;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L;L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.17

T;T;T;T;D

Sift4G

Benign

0.58

T;T;T;T;.

Polyphen

0.039

B;B;B;B;.

Vest4

0.13

MutPred

0.74

Loss of catalytic residue at Q241 (P = 0.0278);Loss of catalytic residue at Q241 (P = 0.0278);Loss of catalytic residue at Q241 (P = 0.0278);Loss of catalytic residue at Q241 (P = 0.0278);.;

MPC

0.41

ClinPred

0.020

GERP RS

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.11

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over