Genetic Variant MNX1:p.Ala127_Ala134dup (chr7-157009949-A-AGCGGCGGCGGCGGCGGCGGCGGCG) – 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.378_401dupCGCCGCCGCCGCCGCCGCCGCCGC(p.Ala127_Ala134dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A134A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MNX1
NM_005515.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

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:

Genome browser will be placed here

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4 link	c.378_401dupCGCCGCCGCCGCCGCCGCCGCCGC	p.Ala127_Ala134dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000252971.11	NP_005506.3	P50219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MNX1	ENST00000252971.11 link	c.378_401dupCGCCGCCGCCGCCGCCGCCGCCGC	p.Ala127_Ala134dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1-AS1	ENST00000818900.1 link	n.296+1910_296+1933dupGGCGGCGGCGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1 link	n.50+825_50+848dupGGCGGCGGCGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0000154

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:

0.0000165

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000642

AC:

AN:

778500

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14820

American (AMR)

AF:

0.00

AC:

AN:

1346

Ashkenazi Jewish (ASJ)

AF:

0.000200

AC:

AN:

4992

East Asian (EAS)

AF:

0.00

AC:

AN:

4308

South Asian (SAS)

AF:

0.00

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:

707980

Other (OTH)

AF:

0.00

AC:

AN:

25952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000154

AC:

AN:

129766

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

62912

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

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:

0.0000165

AC:

AN:

60526

Other (OTH)

AF:

0.00

AC:

AN:

1798

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=69/31

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over