chr7-157009949-AGCGGCG-A

Position:

• chr7-157009949-AGCGGCG-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.396_401delCGCCGC​(p.Ala133_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 0.0018 in 908,126 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (4 hom.)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 2.71

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-AGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 591761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0016 (208/129768) while in subpopulation NFE AF= 0.00207 (125/60510). AF 95% confidence interval is 0.00177. There are 0 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.396_401delCGCCGC	p.Ala133_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.396_401delCGCCGC	p.Ala133_Ala134del	disruptive_inframe_deletion	1/3	1	NM_005515.4	ENSP00000252971.5

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 208 AN: 129760 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000571

Gnomad AMI AF: 0.0664

Gnomad AMR AF: 0.000223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000480

Gnomad SAS AF: 0.00157

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.000556

GnomAD4 exome AF: 0.00183 AC: 1423 AN: 778358 Hom.: 4 AF XY: 0.00184 AC XY: 670 AN XY: 363640

Gnomad4 AFR exome AF: 0.000270

Gnomad4 AMR exome AF: 0.000743

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.00160 AC: 208 AN: 129768 Hom.: 0 Cov.: 0 AF XY: 0.00127 AC XY: 80 AN XY: 62920

Gnomad4 AFR AF: 0.000570

Gnomad4 AMR AF: 0.000222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000482

Gnomad4 SAS AF: 0.00157

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00207

Gnomad4 OTH AF: 0.000554

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -
Uncertain significance, no assertion criteria provided	research	Gharavi Laboratory, Columbia University	Sep 16, 2018	- -

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;