rs781846729

Variant names:

• chr17-28331877-A-C
• rs781846729
• NM_001267776.2:c.109T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-28331877-A-C
• chr17-28331877-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001267776.2(IFT20):​c.109T>G​(p.Cys37Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C37R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT20 NM_001267776.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.43

Genes affected

IFT20 (HGNC:30989): (intraflagellar transport 20) This gene encodes a intraflagellar transport protein important for intracellular transport. The encoded protein forms part of a complex involved in trafficking of proteins from the Golgi body, including recycling of immune signalling components (Finetti et al., PubMed: 19855387). This gene is part of a complex set of sense-antisense loci that may be co-regulated. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome 14.[provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT20	NM_001267776.2	c.109T>G	p.Cys37Gly	missense_variant	Exon 2 of 5	ENST00000395418.8	NP_001254705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT20	ENST00000395418.8	c.109T>G	p.Cys37Gly	missense_variant	Exon 2 of 5	1	NM_001267776.2	ENSP00000378809.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Uncertain	0.73	.;.;.;.;D;.;D;T;.;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D;.;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.1	.;M;.;M;M;.;M;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.2	.;.;.;D;D;.;.;.;.;.
REVEL	Pathogenic	0.70
Sift	Uncertain	0.017	.;.;.;D;D;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;.
Polyphen		1.0	.;.;.;D;D;D;D;.;.;.
Vest4		0.96
MutPred		0.58		Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);.;Gain of loop (P = 0.0051);Gain of loop (P = 0.0051);.;Gain of loop (P = 0.0051);.;.;.;
MVP		0.56
MPC		0.51
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.96
gMVP		0.65

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: rs781846729; hg19: chr17-26658903;