3-129495459-G-C

Variant names:

• chr3-129495459-G-C
• NM_052989.3:c.2060G>C

Variant summary

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

The NM_052989.3(IFT122):​c.2060G>C​(p.Arg687Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R687Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IFT122 NM_052989.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

Genes affected

IFT122 (HGNC:13556): (intraflagellar transport 122) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This cytoplasmic protein contains seven WD repeats and an AF-2 domain which function by recruiting coregulatory molecules and in transcriptional activation. Mutations in this gene cause cranioectodermal dysplasia-1. A related pseudogene is located on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT122	NM_052989.3	c.2060G>C	p.Arg687Pro	missense_variant	Exon 18 of 30	ENST00000348417.7	NP_443715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7	c.2060G>C	p.Arg687Pro	missense_variant	Exon 18 of 30	1	NM_052989.3	ENSP00000324005.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461576 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727080

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	.;.;.;.;.;.;.;D;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.087	D
MutationAssessor	Uncertain	2.8	.;.;.;.;.;.;.;M;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.024	D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.063	T;T;T;T;T;D;T;T;D;D
Polyphen		0.83, 0.97	.;.;P;.;.;.;.;D;.;.
Vest4		0.59
MutPred		0.40		.;.;.;.;.;.;.;Gain of loop (P = 0.0435);.;.;
MVP		0.84
MPC		0.83
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.44
gMVP		0.71

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: chr3-129214302;