Variant 7-157009006-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000252971.11(MNX1):c.691+654C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,537,042 control chromosomes in the GnomAD database, including 659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 102 hom., cov: 33)

Exomes 𝑓: 0.024 ( 557 hom. )

Consequence

MNX1
ENST00000252971.11 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.511

Variant links:

Genes affected

MNX1 (HGNC:4979): (motor neuron and pancreas homeobox 1) This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

MNX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016897321).

BP6

Variant 7-157009006-G-T is Benign according to our data. Variant chr7-157009006-G-T is described in ClinVar as [Benign]. Clinvar id is 1258865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157009006-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.691+654C>A		intron_variant		ENST00000252971.11	NP_005506.3
MNX1	NM_001165255.2 linkuse as main transcript	c.47C>A	p.Ala16Asp	missense_variant	1/3		NP_001158727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11 linkuse as main transcript	c.691+654C>A		intron_variant		1	NM_005515.4	ENSP00000252971	P2	P50219-1

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3134

AN:

152214

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00497

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.0368

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0292

AC:

4209

AN:

144202

Hom.:

187

AF XY:

0.0298

AC XY:

2292

AN XY:

77026

show subpopulations

Gnomad AFR exome

AF:

0.00553

Gnomad AMR exome

AF:

0.00875

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0265

GnomAD4 exome

AF:

0.0237

AC:

32875

AN:

1384710

Hom.:

557

Cov.:

AF XY:

0.0238

AC XY:

16233

AN XY:

683282

show subpopulations

Gnomad4 AFR exome

AF:

0.00408

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.0951

Gnomad4 SAS exome

AF:

0.0282

Gnomad4 FIN exome

AF:

0.0296

Gnomad4 NFE exome

AF:

0.0220

Gnomad4 OTH exome

AF:

0.0290

GnomAD4 genome

AF:

0.0206

AC:

3132

AN:

152332

Hom.:

102

Cov.:

AF XY:

0.0218

AC XY:

1624

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.0360

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0194

TwinsUK

AF:

0.0213

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.00867

AC:

ESP6500EA

AF:

0.0198

AC:

ExAC

AF:

0.0228

AC:

545

Asia WGS

AF:

0.0740

AC:

261

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

3.4

DANN

Benign

0.62

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.27

T;T;.;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

4.2

.;N;D;N

REVEL

Benign

0.12

Sift

Benign

1.0

.;T;.;T

Sift4G

Benign

0.78

.;T;.;.

Vest4

0.056

ClinPred

0.000022

GERP RS

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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