chr7-157009949-AGCGGCGGCGGCG-A

Position:

• chr7-157009949-AGCGGCGGCGGCG-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_005515.4(MNX1):​c.390_401delCGCCGCCGCCGC​(p.Ala131_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 0.00337 in 908,244 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (6 hom.)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.14

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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005515.4
• BP6: Variant 7-157009949-AGCGGCGGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCGGCGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1644782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00197 (256/129774) while in subpopulation NFE AF= 0.00332 (201/60514). AF 95% confidence interval is 0.00294. There are 0 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 256 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.390_401delCGCCGCCGCCGC	p.Ala131_Ala134del	disruptive_inframe_deletion	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_401delCGCCGCCGCCGC	p.Ala131_Ala134del	disruptive_inframe_deletion	1/3	1	NM_005515.4	ENSP00000252971.5

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 256 AN: 129766 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000371

Gnomad ASJ AF: 0.00124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.000748

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.000556

GnomAD4 exome AF: 0.00360 AC: 2805 AN: 778470 Hom.: 6 AF XY: 0.00354 AC XY: 1289 AN XY: 363714

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.000743

Gnomad4 ASJ exome AF: 0.00120

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000556

Gnomad4 FIN exome AF: 0.00373

Gnomad4 NFE exome AF: 0.00386

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00197 AC: 256 AN: 129774 Hom.: 0 Cov.: 0 AF XY: 0.00186 AC XY: 117 AN XY: 62922

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.000370

Gnomad4 ASJ AF: 0.00124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.000748

Gnomad4 NFE AF: 0.00332

Gnomad4 OTH AF: 0.000554

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

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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;