7-157009949-AGCGGCGGCGGCGGCG-AGCGGCG

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_005515.4(MNX1):​c.393_401delCGCCGCCGC​(p.Ala132_Ala134del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 908,220 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.14
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_005515.4
BP6
Variant 7-157009949-AGCGGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1651300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000185 (24/129774) while in subpopulation EAS AF= 0.00193 (8/4146). AF 95% confidence interval is 0.000959. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MNX1NM_005515.4 linkc.393_401delCGCCGCCGC p.Ala132_Ala134del disruptive_inframe_deletion 1/3 ENST00000252971.11 NP_005506.3 P50219-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MNX1ENST00000252971.11 linkc.393_401delCGCCGCCGC p.Ala132_Ala134del disruptive_inframe_deletion 1/31 NM_005515.4 ENSP00000252971.5 P50219-1

Frequencies

GnomAD3 genomes
AF:
0.000185
AC:
24
AN:
129766
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000285
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000742
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000215
Gnomad OTH
AF:
0.000556
GnomAD4 exome
AF:
0.000163
AC:
127
AN:
778446
Hom.:
1
AF XY:
0.000124
AC XY:
45
AN XY:
363696
show subpopulations
Gnomad4 AFR exome
AF:
0.000135
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00116
Gnomad4 SAS exome
AF:
0.000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000120
Gnomad4 OTH exome
AF:
0.00123
GnomAD4 genome
AF:
0.000185
AC:
24
AN:
129774
Hom.:
0
Cov.:
0
AF XY:
0.000111
AC XY:
7
AN XY:
62922
show subpopulations
Gnomad4 AFR
AF:
0.0000285
Gnomad4 AMR
AF:
0.0000741
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000215
Gnomad4 OTH
AF:
0.000554

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 24, 2024- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2023MNX1: PM4, BS1, BS2 -
Currarino triad Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 28, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs548755417; hg19: chr7-156802643; API