Variant 7-157009949-AGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCG 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_401dupCGC(p.Ala134dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 812,940 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 0)

Exomes 𝑓: 0.012 ( 6 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

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:

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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-A-AGCG is Benign according to our data. Variant chr7-157009949-A-AGCG is described in ClinVar as [Likely_benign]. Clinvar id is 211505.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 = 0.00137 (178/129760) while in subpopulation EAS AF= 0.00314 (13/4146). AF 95% confidence interval is 0.00211. There are 2 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4 linkuse as main transcript	c.399_401dupCGC	p.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.399_401dupCGC	p.Ala134dup	disruptive_inframe_insertion	1/3	1	NM_005515.4	ENSP00000252971.5		P50219-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

178

AN:

129752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.000311

Gnomad EAS

AF:

0.00312

Gnomad SAS

AF:

0.000524

Gnomad FIN

AF:

0.000150

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00167

GnomAD4 exome

AF:

0.0120

AC:

8194

AN:

683180

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

3913

AN XY:

319008

show subpopulations

Gnomad4 AFR exome

AF:

0.00896

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00776

Gnomad4 SAS exome

AF:

0.00749

Gnomad4 FIN exome

AF:

0.00386

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00137

AC:

178

AN:

129760

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

AN XY:

62916

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00282

Gnomad4 ASJ

AF:

0.000311

Gnomad4 EAS

AF:

0.00314

Gnomad4 SAS

AF:

0.000525

Gnomad4 FIN

AF:

0.000150

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 14, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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