Variant 7-157008993-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000252971.11(MNX1):c.691+667C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00883 in 1,537,108 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0090 ( 90 hom. )

Consequence

MNX1
ENST00000252971.11 intron

Scores

Splicing: ADA: 0.00003801

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.45

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-157008993-G-T is Benign according to our data. Variant chr7-157008993-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658281.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00698 (1064/152360) while in subpopulation NFE AF= 0.0107 (725/68032). AF 95% confidence interval is 0.01. There are 6 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1064 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.691+667C>A		intron_variant		ENST00000252971.11	NP_005506.3
MNX1	NM_001165255.2 linkuse as main transcript	c.55+5C>A		splice_donor_5th_base_variant, intron_variant			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+667C>A		intron_variant		1	NM_005515.4	ENSP00000252971	P2	P50219-1

Frequencies

GnomAD3 genomes

AF:

0.00698

AC:

1063

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00884

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00642

AC:

925

AN:

144144

Hom.:

AF XY:

0.00671

AC XY:

517

AN XY:

77008

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00452

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00836

Gnomad FIN exome

AF:

0.00827

Gnomad NFE exome

AF:

0.00911

Gnomad OTH exome

AF:

0.00796

GnomAD4 exome

AF:

0.00904

AC:

12516

AN:

1384748

Hom.:

Cov.:

AF XY:

0.00913

AC XY:

6236

AN XY:

683328

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00949

Gnomad4 FIN exome

AF:

0.00865

Gnomad4 NFE exome

AF:

0.00996

Gnomad4 OTH exome

AF:

0.00722

GnomAD4 genome

AF:

0.00698

AC:

1064

AN:

152360

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

504

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.00884

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00882

Hom.:

Bravo

AF:

0.00606

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

MNX1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.19

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

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