22-35067169-AGC-GGG

Variant names:

• chr22-35067169-AGC-GGG
• NM_001303508.2:c.82_84delAGCinsGGG
• ISX p.Ser28Gly

Variant summary

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

The NM_001303508.2(ISX):​c.82_84delAGCinsGGG​(p.Ser28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ISX NM_001303508.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• Publications: 0 publications found

Genes affected

ISX (HGNC:28084): (intestine specific homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the RAXLX homeobox gene family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303508.2. 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
	ISX	NM_001303508.2	MANE Select	c.82_84delAGCinsGGG	p.Ser28Gly	missense	N/A	NP_001290437.1	Q2M1V0
	ISX	NM_001438732.1		c.82_84delAGCinsGGG	p.Ser28Gly	missense	N/A	NP_001425661.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISX	ENST00000404699.7	TSL:1 MANE Select	c.82_84delAGCinsGGG	p.Ser28Gly	missense	N/A	ENSP00000386037.1	Q2M1V0
	ISX	ENST00000308700.6	TSL:1	c.82_84delAGCinsGGG	p.Ser28Gly	missense	N/A	ENSP00000311492.6	Q2M1V0
	ISX	ENST00000885876.1		c.82_84delAGCinsGGG	p.Ser28Gly	missense	N/A	ENSP00000555935.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-35463162;