16-54932668-C-T

Position:

• chr16-54932668-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005853.6(IRX5):​c.420C>T​(p.Tyr140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRX5 NM_005853.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.72

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 16-54932668-C-T is Benign according to our data. Variant chr16-54932668-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2096588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.72 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX5	NM_005853.6	c.420C>T	p.Tyr140=	synonymous_variant	2/3	ENST00000394636.9	NP_005844.4
IRX5	NM_001252197.1	c.420C>T	p.Tyr140=	synonymous_variant	2/3		NP_001239126.1
IRX5	XM_011522809.1	c.210C>T	p.Tyr70=	synonymous_variant	2/3		XP_011521111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRX5	ENST00000394636.9	c.420C>T	p.Tyr140=	synonymous_variant	2/3	3	NM_005853.6	ENSP00000378132	A1
IRX5	ENST00000320990.9	c.420C>T	p.Tyr140=	synonymous_variant	2/3	1		ENSP00000316250	P4
IRX5	ENST00000558597.1	n.597C>T		non_coding_transcript_exon_variant	1/2	1
IRX5	ENST00000560154.5	c.405+459C>T		intron_variant		5		ENSP00000453660

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.95

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: chr16-54966580;