7-157009949-AGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCG

Position:

• chr7-157009949-AGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Likely benign. Variant got -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. Variant has been reported in ClinVar as 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.390_401dupCGCCGCCGCCGC	p.Ala131_Ala134dup	disruptive_inframe_insertion	1/3	ENST00000252971.11	NP_005506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11	c.390_401dupCGCCGCCGCCGC	p.Ala131_Ala134dup	disruptive_inframe_insertion	1/3	1	NM_005515.4	ENSP00000252971.5

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

Gnomad4 AFR exome AF: 0.0310

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00561

Gnomad4 EAS exome AF: 0.00580

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.00149

Gnomad4 NFE exome AF: 0.00744

Gnomad4 OTH exome AF: 0.00732

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

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.00645

Gnomad4 ASJ AF: 0.00747

Gnomad4 EAS AF: 0.00651

Gnomad4 SAS AF: 0.00131

Gnomad4 FIN AF: 0.00449

Gnomad4 NFE AF: 0.00724

Gnomad4 OTH AF: 0.00941

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs548755417; hg19: chr7-156802643;