Genetic Variant NM_005515.4:c.390_401delCGCCGCCGCCGC (chr7-157009949-AGCGGCGGCGGCG-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2

The NM_005515.4(MNX1):c.390_401delCGCCGCCGCCGC(p.Ala131_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 0.00337 in 908,244 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0036 ( 6 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B: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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005515.4

BP6

Variant 7-157009949-AGCGGCGGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCGGCGGCG-A is described in CliVar as Likely_benign. Clinvar id is 1644782.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-157009949-AGCGGCGGCGGCG-A is described in CliVar as Likely_benign. Clinvar id is 1644782.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00197 (256/129774) while in subpopulation NFE AF = 0.00332 (201/60514). AF 95% confidence interval is 0.00294. There are 0 homozygotes in GnomAd4. There are 117 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4 link	c.390_401delCGCCGCCGCCGC	p.Ala131_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.390_401delCGCCGCCGCCGC	p.Ala131_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1-AS1	ENST00000818900.1 link	n.296+1922_296+1933delGGCGGCGGCGGC		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1 link	n.50+837_50+848delGGCGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

256

AN:

129766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000371

Gnomad ASJ

AF:

0.00124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.000748

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.000556

GnomAD4 exome

AF:

0.00360

AC:

2805

AN:

778470

Hom.:

AF XY:

0.00354

AC XY:

1289

AN XY:

363714

show subpopulations

African (AFR)

AF:

0.000270

AC:

AN:

14820

American (AMR)

AF:

0.000743

AC:

AN:

1346

Ashkenazi Jewish (ASJ)

AF:

0.00120

AC:

AN:

4992

East Asian (EAS)

AF:

0.00

AC:

AN:

4306

South Asian (SAS)

AF:

0.000556

AC:

AN:

16176

European-Finnish (FIN)

AF:

0.00373

AC:

AN:

1340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1586

European-Non Finnish (NFE)

AF:

0.00386

AC:

2733

AN:

707952

Other (OTH)

AF:

0.00181

AC:

AN:

25952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

129

258

387

516

645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.00197

AC:

256

AN:

129774

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

117

AN XY:

62922

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

35094

American (AMR)

AF:

0.000370

AC:

AN:

13498

Ashkenazi Jewish (ASJ)

AF:

0.00124

AC:

AN:

3214

East Asian (EAS)

AF:

0.00

AC:

AN:

4146

South Asian (SAS)

AF:

0.00105

AC:

AN:

3814

European-Finnish (FIN)

AF:

0.000748

AC:

AN:

6688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00332

AC:

201

AN:

60514

Other (OTH)

AF:

0.000554

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000441

Hom.:

1464

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

3.1

Mutation Taster

=189/11

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over