NM_005515.4:c.390_401dupCGCCGCCGCCGC

Variant names:

• chr7-157009949-A-AGCGGCGGCGGCG
• rs548755417
• NM_005515.4:c.390_401dupCGCCGCCGCCGC

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_005515.4(MNX1):​c.390_401dupCGCCGCCGCCGC​(p.Ala131_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. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A134A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.014 (38 hom., cov: 0)
  • Exomes 𝑓: 0.0077 (62 hom.)
  • Failed GnomAD Quality Control
• Consequence: MNX1 NM_005515.4 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54
• Publications: 4 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005515.4
• BP6: Variant 7-157009949-A-AGCGGCGGCGGCG is Benign according to our data. Variant chr7-157009949-A-AGCGGCGGCGGCG is described in CliVar as Benign. Clinvar id is 1168422.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-157009949-A-AGCGGCGGCGGCG is described in CliVar as Benign. Clinvar id is 1168422.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4	c.390_401dupCGCCGCCGCCGC	p.Ala131_Ala134dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000252971.11	NP_005506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11	c.390_401dupCGCCGCCGCCGC	p.Ala131_Ala134dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5
MNX1-AS1	ENST00000818900.1	n.296+1922_296+1933dupGGCGGCGGCGGC		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1	n.50+837_50+848dupGGCGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 1783 AN: 129738 Hom.: 37 Cov.: 0

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.00909

Gnomad AMR AF: 0.00638

Gnomad ASJ AF: 0.00747

Gnomad EAS AF: 0.00648

Gnomad SAS AF: 0.00131

Gnomad FIN AF: 0.00449

Gnomad MID AF: 0.00806

Gnomad NFE AF: 0.00724

Gnomad OTH AF: 0.00945

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00771 AC: 6003 AN: 778268 Hom.: 62 Cov.: 28 AF XY: 0.00755 AC XY: 2745 AN XY: 363624

African (AFR) AF: 0.0310 AC: 459 AN: 14804

American (AMR) AF: 0.00297 AC: 4 AN: 1346

Ashkenazi Jewish (ASJ) AF: 0.00561 AC: 28 AN: 4990

East Asian (EAS) AF: 0.00580 AC: 25 AN: 4308

South Asian (SAS) AF: 0.00148 AC: 24 AN: 16176

European-Finnish (FIN) AF: 0.00149 AC: 2 AN: 1340

Middle Eastern (MID) AF: 0.00378 AC: 6 AN: 1586

European-Non Finnish (NFE) AF: 0.00744 AC: 5265 AN: 707776

Other (OTH) AF: 0.00732 AC: 190 AN: 25942

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0138 AC: 1787 AN: 129746 Hom.: 38 Cov.: 0 AF XY: 0.0129 AC XY: 814 AN XY: 62912

African (AFR) AF: 0.0328 AC: 1150 AN: 35076

American (AMR) AF: 0.00645 AC: 87 AN: 13496

Ashkenazi Jewish (ASJ) AF: 0.00747 AC: 24 AN: 3214

East Asian (EAS) AF: 0.00651 AC: 27 AN: 4146

South Asian (SAS) AF: 0.00131 AC: 5 AN: 3814

European-Finnish (FIN) AF: 0.00449 AC: 30 AN: 6688

Middle Eastern (MID) AF: 0.00870 AC: 2 AN: 230

European-Non Finnish (NFE) AF: 0.00724 AC: 438 AN: 60506

Other (OTH) AF: 0.00941 AC: 17 AN: 1806

Alfa AF: 0.00691 Hom.: 1464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=69/31	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs548755417; hg19: chr7-156802643;