rs361863

Variant names:

• chr22-35067169-A-C
• rs361863
• NM_001303508.2:c.82A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-35067169-A-C
• chr22-35067169-A-G
• chr22-35067169-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303508.2(ISX):​c.82A>C​(p.Ser28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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: 22 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07810038).

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.82A>C	p.Ser28Arg	missense	Exon 2 of 5	NP_001290437.1	Q2M1V0
	ISX	NM_001438732.1		c.82A>C	p.Ser28Arg	missense	Exon 1 of 4	NP_001425661.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISX	ENST00000404699.7	TSL:1 MANE Select	c.82A>C	p.Ser28Arg	missense	Exon 2 of 5	ENSP00000386037.1	Q2M1V0
	ISX	ENST00000308700.6	TSL:1	c.82A>C	p.Ser28Arg	missense	Exon 1 of 4	ENSP00000311492.6	Q2M1V0
	ISX	ENST00000885876.1		c.82A>C	p.Ser28Arg	missense	Exon 1 of 4	ENSP00000555935.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
PhyloP100		0.48
Varity_R		0.17
gMVP		0.44
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

dbSNP: rs361863; hg19: chr22-35463162;