7-157009859-G-T

Variant names:

• chr7-157009859-G-T
• rs121912547
• NM_005515.4:c.492C>A

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_005515.4(MNX1):​c.492C>A​(p.Tyr164*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MNX1 NM_005515.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.38
• Publications: 1 publications found

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]

MNX1-AS1 (HGNC:48954): (MNX1 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-157009859-G-T is Pathogenic according to our data. Variant chr7-157009859-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 14853.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MNX1	NM_005515.4	c.492C>A	p.Tyr164*	stop_gained	Exon 1 of 3	ENST00000252971.11	NP_005506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11	c.492C>A	p.Tyr164*	stop_gained	Exon 1 of 3	1	NM_005515.4	ENSP00000252971.5
MNX1-AS1	ENST00000818900.1	n.296+1814G>T		intron_variant	Intron 1 of 1
MNX1-AS1	ENST00000818901.1	n.50+729G>T		intron_variant	Intron 1 of 1
MNX1	ENST00000479817.1	c.-163C>A		upstream_gene_variant		1		ENSP00000474286.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1338908 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 660420

African (AFR) AF: 0.00 AC: 0 AN: 26972

American (AMR) AF: 0.00 AC: 0 AN: 30032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23534

East Asian (EAS) AF: 0.00 AC: 0 AN: 30608

South Asian (SAS) AF: 0.00 AC: 0 AN: 74580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3930

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060252

Other (OTH) AF: 0.00 AC: 0 AN: 55626

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Currarino triad Pathogenic:1

Dec 01, 1998

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.27
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		2.4
Vest4		0.84
GERP RS		0.12
PromoterAI		0.031	Neutral
Mutation Taster		=3/197	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs121912547; hg19: chr7-156802553;