7-123469359-G-T

Position:

• chr7-123469359-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178827.5(IQUB):​c.1436C>A​(p.Thr479Asn) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IQUB NM_178827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

Genes affected

IQUB (HGNC:21995): (IQ motif and ubiquitin domain containing) Predicted to be involved in cilium assembly. Predicted to act upstream of or within smoothened signaling pathway. Predicted to be active in acrosomal vesicle and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1021319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQUB	NM_178827.5	c.1436C>A	p.Thr479Asn	missense_variant	9/13	ENST00000324698.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQUB	ENST00000324698.11	c.1436C>A	p.Thr479Asn	missense_variant	9/13	1	NM_178827.5	P1
IQUB	ENST00000466202.5	c.1436C>A	p.Thr479Asn	missense_variant	9/13	1		P1
IQUB	ENST00000484508.5	c.1436C>A	p.Thr479Asn	missense_variant, NMD_transcript_variant	9/14	2
IQUB	ENST00000469057.1	c.1260C>A	p.Asn420Lys	missense_variant, NMD_transcript_variant	8/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 12, 2024

The c.1436C>A (p.T479N) alteration is located in exon 9 (coding exon 8) of the IQUB gene. This alteration results from a C to A substitution at nucleotide position 1436, causing the threonine (T) at amino acid position 479 to be replaced by an asparagine (N). 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	Benign	0.097
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.26
DEOGEN2	Benign	0.0066	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.85
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.066
Sift	Benign	0.19	T;T
Sift4G	Benign	0.071	T;T
Polyphen		0.049	B;B
Vest4		0.32
MutPred		0.22		Loss of phosphorylation at T479 (P = 0.0401);Loss of phosphorylation at T479 (P = 0.0401);
MVP		0.24
MPC		0.030
ClinPred		0.14	T
GERP RS		1.8
Varity_R		0.074
gMVP		0.30

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

Other links and lift over

dbSNP: rs1257260678; hg19: chr7-123109413;