NM_001023570.4:c.1720G>T

Variant names:

• chr3-121770422-C-A
• rs1201232022
• NM_001023570.4:c.1720G>T

Variant summary

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

The NM_001023570.4(IQCB1):​c.1720G>T​(p.Asp574Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IQCB1 NM_001023570.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

Genes affected

IQCB1 (HGNC:28949): (IQ motif containing B1) This gene encodes a nephrocystin protein that interacts with calmodulin and the retinitis pigmentosa GTPase regulator protein. The encoded protein has a central coiled-coil region and two calmodulin-binding IQ domains. It is localized to the primary cilia of renal epithelial cells and connecting cilia of photoreceptor cells. The protein is thought to play a role in ciliary function. Defects in this gene result in Senior-Loken syndrome type 5. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Jan 2016]

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=0.2258088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4	c.1720G>T	p.Asp574Tyr	missense_variant	Exon 15 of 15	ENST00000310864.11	NP_001018864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11	c.1720G>T	p.Asp574Tyr	missense_variant	Exon 15 of 15	1	NM_001023570.4	ENSP00000311505.6
IQCB1	ENST00000349820.10	c.1321G>T	p.Asp441Tyr	missense_variant	Exon 12 of 12	1		ENSP00000323756.7
IQCB1	ENST00000393650.7	n.*698G>T		non_coding_transcript_exon_variant	Exon 14 of 14	5		ENSP00000377261.3
IQCB1	ENST00000393650.7	n.*698G>T		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000377261.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.89	P;D
Vest4		0.27
MutPred		0.32		Gain of sheet (P = 0.0061);.;
MVP		0.38
MPC		0.41
ClinPred		0.93	D
GERP RS		3.7
Varity_R		0.24
gMVP		0.31

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: rs1201232022; hg19: chr3-121489269;