rs374667274

Variant names:

• chr13-20567992-A-C
• rs374667274
• ENST00000319980.10:c.16A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-20567992-A-C
• chr13-20567992-A-G

Variant summary

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

The NM_175605.5(IFT88):​c.16A>C​(p.Thr6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 561,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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: 0.0000018 (0 hom.)
• Consequence: IFT88 NM_175605.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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=0.08044806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT88	NM_006531.5	c.-7+736A>C		intron_variant	Intron 1 of 25	ENST00000351808.10	NP_006522.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT88	ENST00000319980.10	c.16A>C	p.Thr6Pro	missense_variant	Exon 3 of 28	1		ENSP00000323580.6
IFT88	ENST00000351808.10	c.-7+736A>C		intron_variant	Intron 1 of 25	1	NM_006531.5	ENSP00000261632.5
IFT88	ENST00000389373.3	c.-12A>C		5_prime_UTR_variant	Exon 2 of 4	4		ENSP00000374024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000671 AC: 1 AN: 148936 Hom.: 0 AF XY: 0.0000127 AC XY: 1 AN XY: 78888

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000173

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000178 AC: 1 AN: 561488 Hom.: 0 Cov.: 0 AF XY: 0.00000330 AC XY: 1 AN XY: 303310

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: 0.00000316

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	3.7
DANN	Benign	0.91
DEOGEN2	Benign	0.082	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.0	N
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Polyphen		0.056	B
Vest4		0.30
MutPred		0.20		Loss of MoRF binding (P = 0.0331);
MVP		0.69
MPC		0.16
ClinPred		0.29	T
GERP RS		0.53
Varity_R		0.34
gMVP		0.13

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: rs374667274; hg19: chr13-21142131;