chr7-157009949-A-AGCGGCG

Position:

• chr7-157009949-A-AGCGGCG

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.396_401dupCGCCGC​(p.Ala133_Ala134dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 905,840 control chromosomes in the GnomAD database, including 239,175 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (39716 hom., cov: 0)
  • Exomes 𝑓: 0.73 (199459 hom.)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely 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-AGCGGCG is Benign according to our data. Variant chr7-157009949-A-AGCGGCG is described in ClinVar as [Likely_benign]. Clinvar id is 211504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.396_401dupCGCCGC	p.Ala133_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.396_401dupCGCCGC	p.Ala133_Ala134dup	disruptive_inframe_insertion	1/3	1	NM_005515.4	ENSP00000252971.5

Frequencies

GnomAD3 genomes AF: 0.775 AC: 100357 AN: 129486 Hom.: 39718 Cov.: 0

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.829

GnomAD4 exome AF: 0.732 AC: 568053 AN: 776346 Hom.: 199459 Cov.: 28 AF XY: 0.729 AC XY: 264413 AN XY: 362704

Gnomad4 AFR exome AF: 0.618

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.775 AC: 100361 AN: 129494 Hom.: 39716 Cov.: 0 AF XY: 0.770 AC XY: 48391 AN XY: 62806

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 14, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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;