Variant 16-54931434-TCTC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_005853.6(IRX5):c.240_242delCTC(p.Ser81del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000158 in 1,587,832 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

IRX5
NM_005853.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 6.46

Variant links:

Genes affected

IRX5 (HGNC:14361): (iroquois homeobox 5) This gene encodes a member of the iroquois homeobox gene family, which are involved in several embryonic developmental processes. Knockout mice lacking this gene show that it is required for retinal cone bipolar cell differentiation, and that it negatively regulates potassium channel gene expression in the heart to ensure coordinated cardiac repolarization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

IRX5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_005853.6. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRX5	NM_005853.6 link	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000394636.9	NP_005844.4	P78411-1
IRX5	NM_001252197.1 link	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3		NP_001239126.1	P78411-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRX5	ENST00000394636.9 link	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	3	NM_005853.6	ENSP00000378132.4	P78411-1
IRX5	ENST00000320990.9 link	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	1		ENSP00000316250.5	P78411-2
IRX5	ENST00000560154.5 link	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	5		ENSP00000453660.1	H0YML8

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

207514

Hom.:

AF XY:

0.000181

AC XY:

AN XY:

116326

show subpopulations

Gnomad AFR exome

AF:

0.0000860

Gnomad AMR exome

AF:

0.000369

Gnomad ASJ exome

AF:

0.000653

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000260

Gnomad OTH exome

AF:

0.000943

GnomAD4 exome

AF:

0.000157

AC:

226

AN:

1435614

Hom.:

AF XY:

0.000167

AC XY:

119

AN XY:

713984

show subpopulations

Gnomad4 AFR exome

AF:

0.000244

Gnomad4 AMR exome

AF:

0.000321

Gnomad4 ASJ exome

AF:

0.000620

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.000403

GnomAD4 genome

AF:

0.000164

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.000219

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.240_242delCTC (p.S81del) alteration is located in exon 1 (coding exon 1) of the IRX5 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.240 and c.242, resulting in the deletion of 1 residue. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Craniofacial dysplasia - osteopenia syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Baylor Genetics

May 01, 2016

Our laboratory reported dual molecular diagnoses in IRX5 (NM_005853.5:c.1362_1368delinsGT; NM_005853.5:c.240_242delCTC; in trans) and HDAC8 (NM_018486.2:c.527A>G) in an individual with delayed motor milestones, short stature, delayed speech, intellectual disability, failure to thrive, hypotonia, dysmorphic features, microcephaly, mild hearing loss, myopia, and skeletal abnormalities. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over