16-55326137-A-AAATGCGTTT

Variant names:

• chr16-55326137-A-AAATGCGTTT
• rs2067217
• NM_024335.3:c.46-199_46-198insAATGCGTTT

Variant summary

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

The NM_024335.3(IRX6):​c.46-199_46-198insAATGCGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 444,116 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: IRX6 NM_024335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 2 publications found

Genes affected

IRX6 (HGNC:14675): (iroquois homeobox 6) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell development; neuron differentiation; and regulation of transcription, DNA-templated. Predicted to act upstream of or within detection of visible light; negative regulation of transcription, DNA-templated; and retina morphogenesis in camera-type eye. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259283 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024335.3. 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
	IRX6	NM_024335.3	MANE Select	c.46-199_46-198insAATGCGTTT		intron	N/A	NP_077311.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	ENST00000290552.8	TSL:1 MANE Select	c.46-199_46-198insAATGCGTTT		intron	N/A	ENSP00000290552.8
	IRX6	ENST00000558315.1	TSL:1	n.211+127_211+128insAATGCGTTT		intron	N/A
	IRX6	ENST00000944938.1		c.46-199_46-198insAATGCGTTT		intron	N/A	ENSP00000614997.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000135 AC: 6 AN: 444116 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 231828

African (AFR) AF: 0.00 AC: 0 AN: 12446

American (AMR) AF: 0.00 AC: 0 AN: 15918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13544

East Asian (EAS) AF: 0.000200 AC: 6 AN: 30058

South Asian (SAS) AF: 0.00 AC: 0 AN: 42540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1934

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 272802

Other (OTH) AF: 0.00 AC: 0 AN: 25556

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 1849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031

Splicing

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

Other links and lift over

dbSNP: rs2067217; hg19: chr16-55360049;