13-20574447-A-G

Variant names:

• chr13-20574447-A-G
• NM_006531.5:c.62A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006531.5(IFT88):​c.62A>G​(p.Asn21Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IFT88 NM_006531.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36643988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT88	NM_006531.5	c.62A>G	p.Asn21Ser	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.62A>G	p.Asn21Ser	missense_variant	Exon 2 of 26	1	NM_006531.5	ENSP00000261632.5
IFT88	ENST00000319980.10	c.89A>G	p.Asn30Ser	missense_variant	Exon 4 of 28	1		ENSP00000323580.6
IFT88	ENST00000389373.3	c.62A>G	p.Asn21Ser	missense_variant	Exon 3 of 4	4		ENSP00000374024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456116 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 724594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 30 of the IFT88 protein (p.Asn30Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IFT88-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N;N;D
REVEL	Benign	0.20
Sift	Uncertain	0.013	D;D;D
Sift4G	Benign	0.17	T;T;D
Polyphen		0.96	.;P;.
Vest4		0.45
MutPred		0.36		.;Gain of catalytic residue at I35 (P = 0.0032);.;
MVP		0.49
MPC		0.16
ClinPred		0.93	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr13-21148586;