Genetic Variant NM_005515.4:c.396_401delCGCCGC (chr7-157009949-AGCGGCG-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.396_401delCGCCGC(p.Ala133_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 0.0018 in 908,126 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

MNX1
NM_005515.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 2.71

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: Benign. The variant received -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005515.4

BP6

Variant 7-157009949-AGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 591761.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0016 (208/129768) while in subpopulation NFE AF = 0.00207 (125/60510). AF 95% confidence interval is 0.00177. There are 0 homozygotes in GnomAd4. There are 80 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4 link	c.396_401delCGCCGC	p.Ala133_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.396_401delCGCCGC	p.Ala133_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5	P50219-1
MNX1-AS1	ENST00000818900.1 link	n.296+1928_296+1933delGGCGGC		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1 link	n.50+843_50+848delGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

208

AN:

129760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000571

Gnomad AMI

AF:

0.0664

Gnomad AMR

AF:

0.000223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000480

Gnomad SAS

AF:

0.00157

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.000556

GnomAD4 exome

AF:

0.00183

AC:

1423

AN:

778358

Hom.:

AF XY:

0.00184

AC XY:

670

AN XY:

363640

show subpopulations

African (AFR)

AF:

0.000270

AC:

AN:

14816

American (AMR)

AF:

0.000743

AC:

AN:

1346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4990

East Asian (EAS)

AF:

0.00

AC:

AN:

4308

South Asian (SAS)

AF:

0.00173

AC:

AN:

16176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1340

Middle Eastern (MID)

AF:

0.00126

AC:

AN:

1586

European-Non Finnish (NFE)

AF:

0.00187

AC:

1327

AN:

707852

Other (OTH)

AF:

0.00235

AC:

AN:

25944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

139

208

278

347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00160

AC:

208

AN:

129768

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

AN XY:

62920

show subpopulations

African (AFR)

AF:

0.000570

AC:

AN:

35094

American (AMR)

AF:

0.000222

AC:

AN:

13498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3214

East Asian (EAS)

AF:

0.000482

AC:

AN:

4146

South Asian (SAS)

AF:

0.00157

AC:

AN:

3814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00207

AC:

125

AN:

60510

Other (OTH)

AF:

0.000554

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.571

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:

0.00

Hom.:

1464

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Mutation Taster

=193/7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over