13-20631053-G-A

Position:

• chr13-20631053-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006531.5(IFT88):​c.1337G>A​(p.Ser446Asn) variant causes a missense change. The variant allele was found at a frequency of 0.741 in 1,601,714 control chromosomes in the GnomAD database, including 444,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.70 (37816 hom., cov: 31)
  • Exomes 𝑓: 0.75 (407153 hom.)
• Consequence: IFT88 NM_006531.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.19

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]

IFT88 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8165531E-6).
• BP6: Variant 13-20631053-G-A is Benign according to our data. Variant chr13-20631053-G-A is described in ClinVar as [Benign]. Clinvar id is 402967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-20631053-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT88	NM_006531.5	c.1337G>A	p.Ser446Asn	missense_variant	16/26	ENST00000351808.10	NP_006522.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT88	ENST00000351808.10	c.1337G>A	p.Ser446Asn	missense_variant	16/26	1	NM_006531.5	ENSP00000261632.5

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105657 AN: 151906 Hom.: 37800 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.719

GnomAD3 exomes AF: 0.770 AC: 193468 AN: 251276 Hom.: 76101 AF XY: 0.774 AC XY: 105169 AN XY: 135826

Gnomad AFR exome AF: 0.530

Gnomad AMR exome AF: 0.853

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.878

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.741

GnomAD4 exome AF: 0.746 AC: 1081023 AN: 1449690 Hom.: 407153 Cov.: 32 AF XY: 0.750 AC XY: 541777 AN XY: 722042

Gnomad4 AFR exome AF: 0.526

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.872

Gnomad4 FIN exome AF: 0.745

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.742

GnomAD4 genome AF: 0.695 AC: 105719 AN: 152024 Hom.: 37816 Cov.: 31 AF XY: 0.704 AC XY: 52335 AN XY: 74304

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.720

Alfa AF: 0.718 Hom.: 50675

Bravo AF: 0.688

TwinsUK AF: 0.739 AC: 2739

ALSPAC AF: 0.725 AC: 2794

ESP6500AA AF: 0.535 AC: 2359

ESP6500EA AF: 0.721 AC: 6202

ExAC AF: 0.760 AC: 92275

Asia WGS AF: 0.914 AC: 3178 AN: 3478

EpiCase AF: 0.723

EpiControl AF: 0.724

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	T;T
MetaRNN	Benign	0.0000018	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.55	.;P
Vest4		0.21
MPC		0.052
ClinPred		0.035	T
GERP RS		4.6
Varity_R		0.29
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs9509307; hg19: chr13-21205192;