NM_005853.6:c.212C>T

Variant names:

• chr16-54931410-C-T
• NM_005853.6:c.212C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005853.6(IRX5):​c.212C>T​(p.Pro71Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000486 in 1,440,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: IRX5 NM_005853.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40528128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRX5	NM_005853.6	c.212C>T	p.Pro71Leu	missense_variant	Exon 1 of 3	ENST00000394636.9	NP_005844.4
IRX5	NM_001252197.1	c.212C>T	p.Pro71Leu	missense_variant	Exon 1 of 3		NP_001239126.1
IRX5	XM_011522809.1	c.-761C>T		upstream_gene_variant			XP_011521111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRX5	ENST00000394636.9	c.212C>T	p.Pro71Leu	missense_variant	Exon 1 of 3	3	NM_005853.6	ENSP00000378132.4
IRX5	ENST00000320990.9	c.212C>T	p.Pro71Leu	missense_variant	Exon 1 of 3	1		ENSP00000316250.5
IRX5	ENST00000560154.5	c.212C>T	p.Pro71Leu	missense_variant	Exon 1 of 3	5		ENSP00000453660.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1440920 Hom.: 0 Cov.: 32 AF XY: 0.00000419 AC XY: 3 AN XY: 716828

Gnomad4 AFR exome AF: 0.00

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: 0.00000631

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	0.0038	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.3	L;.;.;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.2	D;D;.;D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;.;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.96	P;.;D;.
Vest4		0.32
MutPred		0.34		Loss of disorder (P = 0.0215);Loss of disorder (P = 0.0215);Loss of disorder (P = 0.0215);Loss of disorder (P = 0.0215);
MVP		0.73
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.27
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-54965322;