Variant 16-54931410-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005853.6(IRX5):c.212C>G(p.Pro71Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,440,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IRX5
NM_005853.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRX5	NM_005853.6 link	c.212C>G	p.Pro71Arg	missense_variant	Exon 1 of 3	ENST00000394636.9	NP_005844.4	P78411-1
IRX5	NM_001252197.1 link	c.212C>G	p.Pro71Arg	missense_variant	Exon 1 of 3		NP_001239126.1	P78411-2
IRX5	XM_011522809.1 link	c.-761C>G		upstream_gene_variant			XP_011521111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRX5	ENST00000394636.9 link	c.212C>G	p.Pro71Arg	missense_variant	Exon 1 of 3	3	NM_005853.6	ENSP00000378132.4	P78411-1
IRX5	ENST00000320990.9 link	c.212C>G	p.Pro71Arg	missense_variant	Exon 1 of 3	1		ENSP00000316250.5	P78411-2
IRX5	ENST00000560154.5 link	c.212C>G	p.Pro71Arg	missense_variant	Exon 1 of 3	5		ENSP00000453660.1	H0YML8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000459

AC:

AN:

217800

Hom.:

AF XY:

0.00000821

AC XY:

AN XY:

121834

show subpopulations

Gnomad AFR exome

AF:

0.0000808

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1440920

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716828

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000880

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.212C>G (p.P71R) alteration is located in exon 1 (coding exon 1) of the IRX5 gene. This alteration results from a C to G substitution at nucleotide position 212, causing the proline (P) at amino acid position 71 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

D;.;T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

T;T;T;T

M_CAP

Pathogenic

0.65

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.3

L;.;.;L

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-4.1

D;D;.;D

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.42

MutPred

0.33

Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);

MVP

0.77

ClinPred

0.81

GERP RS

3.9

Varity_R

0.45

gMVP

0.77

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