chr16-54286285-G-T

Variant names:

• chr16-54286285-G-T
• rs3751723
• NM_024336.3:c.-235C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024336.3(IRX3):​c.-235C>A variant causes a 5 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.322 in 998,464 control chromosomes in the GnomAD database, including 53,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6817 hom., cov: 32)
  • Exomes 𝑓: 0.33 (46257 hom.)
• Consequence: IRX3 NM_024336.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.27
• Publications: 17 publications found

Genes affected

IRX3 (HGNC:14360): (iroquois homeobox 3) IRX3 is a member of the Iroquois homeobox gene family (see IRX1; MIM 606197) and plays a role in an early step of neural development (Bellefroid et al., 1998 [PubMed 9427753]). Members of this family appear to play multiple roles during pattern formation of vertebrate embryos (Lewis et al., 1999 [PubMed 10370142]).[supplied by OMIM, Aug 2009]

ENSG00000287885 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024336.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX3	NM_024336.3	MANE Select	c.-235C>A		5_prime_UTR	Exon 1 of 4	NP_077312.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX3	ENST00000329734.4	TSL:1 MANE Select	c.-235C>A		5_prime_UTR	Exon 1 of 4	ENSP00000331608.3
	ENSG00000287885	ENST00000637770.2	TSL:1	n.77+626G>T		intron	N/A
	IRX3	ENST00000558180.2	TSL:4	n.46+394C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43652 AN: 151834 Hom.: 6821 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.328 AC: 277871 AN: 846512 Hom.: 46257 Cov.: 34 AF XY: 0.328 AC XY: 128618 AN XY: 392514

African (AFR) AF: 0.149 AC: 2375 AN: 15990

American (AMR) AF: 0.318 AC: 462 AN: 1452

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 1504 AN: 5422

East Asian (EAS) AF: 0.524 AC: 2101 AN: 4008

South Asian (SAS) AF: 0.357 AC: 6074 AN: 17012

European-Finnish (FIN) AF: 0.242 AC: 453 AN: 1870

Middle Eastern (MID) AF: 0.299 AC: 502 AN: 1680

European-Non Finnish (NFE) AF: 0.331 AC: 255123 AN: 771066

Other (OTH) AF: 0.331 AC: 9277 AN: 28012

GnomAD4 genome AF: 0.287 AC: 43653 AN: 151952 Hom.: 6817 Cov.: 32 AF XY: 0.287 AC XY: 21316 AN XY: 74270

African (AFR) AF: 0.159 AC: 6584 AN: 41534

American (AMR) AF: 0.314 AC: 4793 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 997 AN: 3464

East Asian (EAS) AF: 0.511 AC: 2612 AN: 5110

South Asian (SAS) AF: 0.379 AC: 1824 AN: 4818

European-Finnish (FIN) AF: 0.270 AC: 2855 AN: 10572

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22805 AN: 67860

Other (OTH) AF: 0.323 AC: 681 AN: 2106

Alfa AF: 0.324 Hom.: 10497

Bravo AF: 0.286

Asia WGS AF: 0.452 AC: 1567 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.97
PhyloP100		7.3
PromoterAI		0.15	Neutral
Mutation Taster		=294/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3751723; hg19: chr16-54320197; COSMIC: COSV61667968; COSMIC: COSV61667968;