Variant 7-157009949-AGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BS1_SupportingBS2

The NM_005515.4(MNX1):c.387_401dupCGCCGCCGCCGCCGC(p.Ala130_Ala134dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 4 hom., cov: 0)

Exomes 𝑓: 0.00036 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

MNX1
NM_005515.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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 Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005515.4

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00142 (184/129770) while in subpopulation AFR AF= 0.00439 (154/35092). AF 95% confidence interval is 0.00382. There are 4 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.387_401dupCGCCGCCGCCGCCGC	p.Ala130_Ala134dup	disruptive_inframe_insertion	1/3	ENST00000252971.11	NP_005506.3	P50219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11 linkuse as main transcript	c.387_401dupCGCCGCCGCCGCCGC	p.Ala130_Ala134dup	disruptive_inframe_insertion	1/3	1	NM_005515.4	ENSP00000252971.5		P50219-1

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

185

AN:

129762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00442

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000480

Gnomad SAS

AF:

0.000262

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000347

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000361

AC:

281

AN:

778472

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

131

AN XY:

363720

show subpopulations

Gnomad4 AFR exome

AF:

0.00371

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000232

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000283

Gnomad4 OTH exome

AF:

0.000501

GnomAD4 genome

AF:

0.00142

AC:

184

AN:

129770

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

62918

show subpopulations

Gnomad4 AFR

AF:

0.00439

Gnomad4 AMR

AF:

0.000445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000482

Gnomad4 SAS

AF:

0.000262

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000347

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

This variant, c.387_401dup, results in the insertion of 5 amino acid(s) of the MNX1 protein (p.Ala130_Ala134dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MNX1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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.

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