chr7-157006558-TGCTCCA-T

Variant names:

• chr7-157006558-TGCTCCA-T
• NM_005515.4:c.767_772delTGGAGC

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_005515.4(MNX1):​c.767_772delTGGAGC​(p.Leu256_Glu257del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L256L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88
• Publications: 0 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-AS2 (HGNC:40278): (MNX1 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_005515.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005515.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	NM_005515.4	MANE Select	c.767_772delTGGAGC	p.Leu256_Glu257del	disruptive_inframe_deletion	Exon 2 of 3	NP_005506.3
	MNX1	NM_001165255.2		c.131_136delTGGAGC	p.Leu44_Glu45del	disruptive_inframe_deletion	Exon 2 of 3	NP_001158727.1	P50219-2
	MNX1-AS2	NR_147077.1		n.118+143_118+148delTCCAGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	ENST00000252971.11	TSL:1 MANE Select	c.767_772delTGGAGC	p.Leu256_Glu257del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000252971.5	P50219-1
	MNX1	ENST00000543409.5	TSL:1	c.131_136delTGGAGC	p.Leu44_Glu45del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000438552.1	P50219-2
	MNX1	ENST00000428439.1	TSL:1	c.131_136delTGGAGC	p.Leu44_Glu45del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000401158.1	C9K088

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9

Splicing

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

Other links and lift over

hg19: chr7-156799252;