13-20567683-A-C

Variant names:

• chr13-20567683-A-C
• rs9552244
• ENST00000319980.10:c.-195A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_175605.5(IFT88):​c.-195A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 991,202 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: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: IFT88 NM_175605.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175605.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	NM_006531.5	MANE Select	c.-7+427A>C		intron	N/A	NP_006522.2
	IFT88	NM_001318493.2		c.-294A>C		5_prime_UTR	Exon 2 of 27	NP_001305422.1	Q13099-1
	IFT88	NM_001353566.2		c.-186A>C		5_prime_UTR	Exon 2 of 28	NP_001340495.1	Q13099-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	ENST00000319980.10	TSL:1	c.-195A>C		5_prime_UTR	Exon 2 of 28	ENSP00000323580.6	Q13099-1
	IFT88	ENST00000351808.10	TSL:1 MANE Select	c.-7+427A>C		intron	N/A	ENSP00000261632.5	Q13099-2
	IFT88	ENST00000894245.1		c.-321A>C		5_prime_UTR	Exon 1 of 26	ENSP00000564304.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000504 AC: 5 AN: 991202 Hom.: 0 Cov.: 16 AF XY: 0.00000642 AC XY: 3 AN XY: 467118

African (AFR) AF: 0.00 AC: 0 AN: 21518

American (AMR) AF: 0.00 AC: 0 AN: 8078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11556

East Asian (EAS) AF: 0.00 AC: 0 AN: 19018

South Asian (SAS) AF: 0.00 AC: 0 AN: 21998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2406

European-Non Finnish (NFE) AF: 0.00000583 AC: 5 AN: 857888

Other (OTH) AF: 0.00 AC: 0 AN: 37882

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9552244; hg19: chr13-21141822;