13-20574465-A-G

Variant names:

• chr13-20574465-A-G
• rs750818479
• NM_006531.5:c.80A>G

Variant summary

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

The NM_001353579.2(IFT88):​c.-484A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000904 in 1,438,432 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: 0.0000090 (0 hom.)
• Consequence: IFT88 NM_001353579.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

Genes affected

IFT88 (HGNC:20606): (intraflagellar transport 88) This gene encodes a member of the tetratrico peptide repeat (TPR) family. The encoded protein is involved in cilium biogenesis. Mutations of a similar gene in mouse can cause polycystic kidney disease. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2017]

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=0.2057085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT88	NM_006531.5	c.80A>G	p.Tyr27Cys	missense_variant	Exon 2 of 26	ENST00000351808.10	NP_006522.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT88	ENST00000351808.10	c.80A>G	p.Tyr27Cys	missense_variant	Exon 2 of 26	1	NM_006531.5	ENSP00000261632.5
IFT88	ENST00000319980.10	c.107A>G	p.Tyr36Cys	missense_variant	Exon 4 of 28	1		ENSP00000323580.6
IFT88	ENST00000389373.3	c.80A>G	p.Tyr27Cys	missense_variant	Exon 3 of 4	4		ENSP00000374024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 247848 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 133958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000670

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000904 AC: 13 AN: 1438432 Hom.: 0 Cov.: 24 AF XY: 0.0000126 AC XY: 9 AN XY: 716734

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: 0.000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;D;.
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.28
MutPred		0.44		.;Gain of catalytic residue at D31 (P = 0.0054);.;
MVP		0.50
MPC		0.20
ClinPred		0.96	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.50

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: rs750818479; hg19: chr13-21148604;