Genetic Variant NM_005515.4:c.387_401delCGCCGCCGCCGCCGC (chr7-157009949-AGCGGCGGCGGCGGCG-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005515.4(MNX1):c.387_401delCGCCGCCGCCGCCGC(p.Ala130_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 0.00000661 in 908,254 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000077 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

Publications

4 publications found

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:

MNX1-AS1 (HGNC:48954): (MNX1 antisense RNA 1 (head to head))

MNX1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005515.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005515.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	NM_005515.4	MANE Select	c.387_401delCGCCGCCGCCGCCGC	p.Ala130_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	NP_005506.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MNX1	ENST00000252971.11	TSL:1 MANE Select	c.387_401delCGCCGCCGCCGCCGC	p.Ala130_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000252971.5	P50219-1
MNX1-AS1	ENST00000818900.1		n.296+1919_296+1933delGGCGGCGGCGGCGGC		intron	N/A
MNX1-AS1	ENST00000818901.1		n.50+834_50+848delGGCGGCGGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000771

AC:

AN:

129766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000642

AC:

AN:

778488

Hom.:

AF XY:

0.00000550

AC XY:

AN XY:

363726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14820

American (AMR)

AF:

0.00

AC:

AN:

1346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4992

East Asian (EAS)

AF:

0.00

AC:

AN:

4308

South Asian (SAS)

AF:

0.0000618

AC:

AN:

16176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1586

European-Non Finnish (NFE)

AF:

0.00000565

AC:

AN:

707970

Other (OTH)

AF:

0.00

AC:

AN:

25950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000771

AC:

AN:

129766

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

62912

show subpopulations

African (AFR)

AF:

0.0000285

AC:

AN:

35056

American (AMR)

AF:

0.00

AC:

AN:

13482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3214

East Asian (EAS)

AF:

0.00

AC:

AN:

4164

South Asian (SAS)

AF:

0.00

AC:

AN:

3820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60526

Other (OTH)

AF:

0.00

AC:

AN:

1798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

1464

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Currarino triad (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Mutation Taster

=190/10

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over