NM_005515.4:c.399_401delCGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:3

Conservation

PhyloP100: 2.45

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: Benign. The variant received -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 CliVar as Benign/Likely_benign. Clinvar id is 591750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157009949-AGCG-A is described in CliVar as Benign/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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4 link	c.399_401delCGC	p.Ala134del	disruptive_inframe_deletion	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.399_401delCGC	p.Ala134del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1-AS1	ENST00000818900.1 link	n.296+1931_296+1933delGGC		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1 link	n.50+846_50+848delGGC		intron_variant	Intron 1 of 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

African (AFR)

AF:

0.00149

AC:

AN:

14814

American (AMR)

AF:

0.000746

AC:

AN:

1340

Ashkenazi Jewish (ASJ)

AF:

0.00641

AC:

AN:

4990

East Asian (EAS)

AF:

0.00349

AC:

AN:

4300

South Asian (SAS)

AF:

0.00520

AC:

AN:

16154

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

1340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1584

European-Non Finnish (NFE)

AF:

0.00238

AC:

1683

AN:

707438

Other (OTH)

AF:

0.00212

AC:

AN:

25924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

194

291

388

485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.00227

AC:

294

AN:

129770

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

153

AN XY:

62920

show subpopulations

African (AFR)

AF:

0.00162

AC:

AN:

35090

American (AMR)

AF:

0.00244

AC:

AN:

13498

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

AN:

3214

East Asian (EAS)

AF:

0.00193

AC:

AN:

4146

South Asian (SAS)

AF:

0.00603

AC:

AN:

3814

European-Finnish (FIN)

AF:

0.000897

AC:

AN:

6688

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00207

AC:

125

AN:

60514

Other (OTH)

AF:

0.00443

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00132

Hom.:

1464

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2018

Gharavi Laboratory, Columbia University

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MNX1: BP3 -

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.4

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over