7-157009949-AGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCG

Position:

• chr7-157009949-AGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_005515.4(MNX1):​c.401_402insCGCCGCCGC​(p.Ala132_Ala134dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. 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 0.11 (1095 hom., cov: 0)
  • Exomes 𝑓: 0.073 (2158 hom.)
  • Failed GnomAD Quality Control
• Consequence: MNX1 NM_005515.4 inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005515.4
• BP6: Variant 7-157009949-A-AGCGGCGGCG is Benign according to our data. Variant chr7-157009949-A-AGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 1170017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MNX1	NM_005515.4	c.401_402insCGCCGCCGC	p.Ala132_Ala134dup	inframe_insertion	1/3	ENST00000252971.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MNX1	ENST00000252971.11	c.401_402insCGCCGCCGC	p.Ala132_Ala134dup	inframe_insertion	1/3	1	NM_005515.4	P2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 13620 AN: 129580 Hom.: 1092 Cov.: 0

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0701

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.0244

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0729

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0734 AC: 56928 AN: 775888 Hom.: 2158 Cov.: 28 AF XY: 0.0734 AC XY: 26605 AN XY: 362474

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0663

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0695

Gnomad4 OTH exome AF: 0.0812

GnomAD4 genome AF: 0.105 AC: 13623 AN: 129588 Hom.: 1095 Cov.: 0 AF XY: 0.107 AC XY: 6698 AN XY: 62824

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0869

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.0725

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 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;