chr7-123452843-G-A

Position:

• chr7-123452843-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178827.5(IQUB):​c.2276C>T​(p.Ala759Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IQUB NM_178827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.61

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQUB	NM_178827.5	c.2276C>T	p.Ala759Val	missense_variant	13/13	ENST00000324698.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQUB	ENST00000324698.11	c.2276C>T	p.Ala759Val	missense_variant	13/13	1	NM_178827.5	P1
IQUB	ENST00000466202.5	c.2276C>T	p.Ala759Val	missense_variant	13/13	1		P1
IQUB	ENST00000469057.1	c.*834C>T		3_prime_UTR_variant, NMD_transcript_variant	12/12	2
IQUB	ENST00000484508.5	c.*681C>T		3_prime_UTR_variant, NMD_transcript_variant	14/14	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Jul 26, 2022

The c.2276C>T (p.A759V) alteration is located in exon 13 (coding exon 12) of the IQUB gene. This alteration results from a C to T substitution at nucleotide position 2276, causing the alanine (A) at amino acid position 759 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.91	P;P
Vest4		0.53
MutPred		0.75		Loss of catalytic residue at A759 (P = 0.0442);Loss of catalytic residue at A759 (P = 0.0442);
MVP		0.53
MPC		0.14
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.30
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-123092897;