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

Variant summary

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

The NM_005515.4(MNX1):c.399_401delCGC(p.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 0.00241 in 907,654 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 5 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 2.45

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:

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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-AGCG-A is Benign according to our data. Variant chr7-157009949-AGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 591750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00227 (294/129770) while in subpopulation SAS AF= 0.00603 (23/3814). AF 95% confidence interval is 0.00412. There are 2 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 294 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.399_401delCGC	p.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
MNX1	ENST00000252971.11 linkuse as main transcript	c.399_401delCGC	p.Ala134del	disruptive_inframe_deletion	1/3	1	NM_005515.4	ENSP00000252971.5		P50219-1

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

294

AN:

129762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00245

Gnomad ASJ

AF:

0.0103

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.000897

Gnomad MID

AF:

0.00403

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.00445

GnomAD4 exome

AF:

0.00243

AC:

1894

AN:

777884

Hom.:

AF XY:

0.00244

AC XY:

887

AN XY:

363418

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.000746

Gnomad4 ASJ exome

AF:

0.00641

Gnomad4 EAS exome

AF:

0.00349

Gnomad4 SAS exome

AF:

0.00520

Gnomad4 FIN exome

AF:

0.00149

Gnomad4 NFE exome

AF:

0.00238

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00227

AC:

294

AN:

129770

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

153

AN XY:

62920

show subpopulations

Gnomad4 AFR

AF:

0.00162

Gnomad4 AMR

AF:

0.00244

Gnomad4 ASJ

AF:

0.0103

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00603

Gnomad4 FIN

AF:

0.000897

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.00443

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MNX1: BP3 -
Uncertain significance, no assertion criteria provided	research	Gharavi Laboratory, Columbia University	Sep 16, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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