NM_006531.5:c.74C>T

Variant names:

• chr13-20574459-C-T
• NM_006531.5:c.74C>T

Variant summary

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

The NM_006531.5(IFT88):​c.74C>T​(p.Pro25Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 4.73

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT88	NM_006531.5	c.74C>T	p.Pro25Leu	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.74C>T	p.Pro25Leu	missense_variant	Exon 2 of 26	1	NM_006531.5	ENSP00000261632.5
IFT88	ENST00000319980.10	c.101C>T	p.Pro34Leu	missense_variant	Exon 4 of 28	1		ENSP00000323580.6
IFT88	ENST00000389373.3	c.74C>T	p.Pro25Leu	missense_variant	Exon 3 of 4	4		ENSP00000374024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443976 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 719178

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

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 specified Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101C>T (p.P34L) alteration is located in exon 4 (coding exon 2) of the IFT88 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the proline (P) at amino acid position 34 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	.;D;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.061	T;T;D
Polyphen		1.0	.;D;.
Vest4		0.65
MutPred		0.46		.;Gain of catalytic residue at I35 (P = 0.0074);.;
MVP		0.43
MPC		0.28
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr13-21148598;