chr16-54931434-TCTC-T

Variant names:

• chr16-54931434-TCTC-T
• rs776389982
• NM_005853.6:c.240_242delCTC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 6.46
• Publications: 0 publications found

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]

CRNDE (HGNC:37078): (colorectal neoplasia differentially expressed) This gene is transcribed into multiple transcript variants, some of which may function as non-coding RNAs. One of the transcript variants encodes a putative short protein that is localized to the nucleus (PMID:25978564). Expression of this locus is increased in proliferating tissues, including certain tumors such as colorectal adenomas and adenocarcinomas. Transcription from this gene is negatively regulated by insulin and insulin-like growth factors, and may regulate the expression of genes involved in metabolism. [provided by RefSeq, May 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005853.6. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005853.6. 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
	IRX5	NM_005853.6	MANE Select	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	NP_005844.4
	IRX5	NM_001252197.1		c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	NP_001239126.1	P78411-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX5	ENST00000394636.9	TSL:3 MANE Select	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000378132.4	P78411-1
	IRX5	ENST00000320990.9	TSL:1	c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000316250.5	P78411-2
	IRX5	ENST00000967637.1		c.240_242delCTC	p.Ser81del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000637696.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152104 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000231 AC: 48 AN: 207514 AF XY: 0.000181

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 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.: 1 AF XY: 0.000167 AC XY: 119 AN XY: 713984

African (AFR) AF: 0.000244 AC: 8 AN: 32784

American (AMR) AF: 0.000321 AC: 14 AN: 43660

Ashkenazi Jewish (ASJ) AF: 0.000620 AC: 16 AN: 25816

East Asian (EAS) AF: 0.00 AC: 0 AN: 39178

South Asian (SAS) AF: 0.00 AC: 0 AN: 85116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38340

Middle Eastern (MID) AF: 0.00190 AC: 8 AN: 4216

European-Non Finnish (NFE) AF: 0.000141 AC: 156 AN: 1107014

Other (OTH) AF: 0.000403 AC: 24 AN: 59490

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74418

African (AFR) AF: 0.000120 AC: 5 AN: 41548

American (AMR) AF: 0.000327 AC: 5 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000261 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Craniofacial dysplasia - osteopenia syndrome (1)
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs776389982; hg19: chr16-54965346;