Variant 7-73595861-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032951.3(MLXIPL):c.2167G>A(p.Glu723Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,609,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

MLXIPL
NM_032951.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0087403655).

BP6

Variant 7-73595861-C-T is Benign according to our data. Variant chr7-73595861-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 708718.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLXIPL	NM_032951.3 linkuse as main transcript	c.2167G>A	p.Glu723Lys	missense_variant	14/17	ENST00000313375.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLXIPL	ENST00000313375.8 linkuse as main transcript	c.2167G>A	p.Glu723Lys	missense_variant	14/17	1	NM_032951.3	A2	Q9NP71-1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

165

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00127

AC:

305

AN:

239956

Hom.:

AF XY:

0.00133

AC XY:

174

AN XY:

130564

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.000804

Gnomad ASJ exome

AF:

0.00940

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000201

Gnomad FIN exome

AF:

0.000195

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00105

AC:

1523

AN:

1456796

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

765

AN XY:

724440

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000909

Gnomad4 ASJ exome

AF:

0.00935

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.000134

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.00135

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152328

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00203

Hom.:

Bravo

AF:

0.00108

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00101

AC:

122

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.030

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0087

T;T;T;T;T

MetaSVM

Pathogenic

0.99

MutationTaster

Benign

0.93

D;D;D;D;D;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.18

T;T;T;T;T

Sift4G

Uncertain

0.043

D;D;D;D;T

Polyphen

0.97

D;D;D;D;.

Vest4

0.39

MVP

0.58

MPC

0.13

ClinPred

0.043

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.52

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over