NM_001267776.2:c.116A>G

Variant names:

• chr17-28331870-T-C
• NM_001267776.2:c.116A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001267776.2(IFT20):​c.116A>G​(p.Asp39Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D39Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT20 NM_001267776.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30724445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT20	NM_001267776.2	c.116A>G	p.Asp39Gly	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.116A>G	p.Asp39Gly	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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.116A>G (p.D39G) alteration is located in exon 2 (coding exon 1) of the IFT20 gene. This alteration results from a A to G substitution at nucleotide position 116, causing the aspartic acid (D) at amino acid position 39 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	.;.;.;.;D;.;D;T;.;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D;D;D;D;.;D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;.;L;L;.;L;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	.;.;.;D;D;.;.;.;.;.
REVEL	Benign	0.070
Sift	Uncertain	0.029	.;.;.;D;T;.;.;.;.;.
Sift4G	Benign	0.28	T;T;T;T;T;T;T;T;T;.
Polyphen		0.57, 0.16, 0.27	.;.;.;P;B;B;B;.;.;.
Vest4		0.44
MutPred		0.30		Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);.;Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);.;Gain of loop (P = 0.0121);.;.;.;
MVP		0.39
MPC		0.19
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.36
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26658896;