Variant chr16-54285422-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024336.3(IRX3):c.459C>A(p.Pro153Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,170 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 10 hom. )

Consequence

IRX3
NM_024336.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.19

Variant links:

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]

IRX3 links:

IRX3 (HGNC:):

IRX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-54285422-G-T is Benign according to our data. Variant chr16-54285422-G-T is described in ClinVar as [Benign]. Clinvar id is 704001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00648 (987/152306) while in subpopulation AFR AF= 0.0221 (920/41592). AF 95% confidence interval is 0.0209. There are 11 homozygotes in gnomad4. There are 484 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 987 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX3	NM_024336.3 linkuse as main transcript	c.459C>A	p.Pro153Pro	synonymous_variant	2/4	ENST00000329734.4	NP_077312.2	P78415
IRX3	XM_005256139.4 linkuse as main transcript	c.459C>A	p.Pro153Pro	synonymous_variant	2/4		XP_005256196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IRX3	ENST00000329734.4 linkuse as main transcript	c.459C>A	p.Pro153Pro	synonymous_variant	2/4	1	NM_024336.3	ENSP00000331608.3	P78415
IRX3	ENST00000558054.1 linkuse as main transcript	c.72+362C>A		intron_variant		2		ENSP00000463991.1	J3QR11
IRX3	ENST00000558180.2 linkuse as main transcript	n.238C>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

987

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00168

AC:

423

AN:

251484

Hom.:

AF XY:

0.00127

AC XY:

173

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000661

AC:

967

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

406

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00648

AC:

987

AN:

152306

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

484

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00735

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.90

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

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