2-177616777-C-T

Position:

• chr2-177616777-C-T

Variant summary

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

The NM_152275.4(IFT70A):​c.1925G>A​(p.Gly642Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: IFT70A NM_152275.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.77

Genes affected

IFT70A (HGNC:25853): (intraflagellar transport 70A) Predicted to enable intraciliary transport particle B binding activity. Predicted to be involved in intraciliary transport. Predicted to be located in centrosome and cilium. Predicted to be part of intraciliary transport particle B. Predicted to be active in axonemal microtubule and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000237655 (HGNC:):

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/exons	MANE	Protein	UniProt
IFT70A	NM_152275.4	c.1925G>A	p.Gly642Glu	missense_variant	1/1	ENST00000355689.6	NP_689488.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC30A	ENST00000355689.6	c.1925G>A	p.Gly642Glu	missense_variant	1/1	6	NM_152275.4	ENSP00000347915.4
ENSG00000237655	ENST00000357045.4	n.86-524C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152184 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74472

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.1925G>A (p.G642E) alteration is located in exon 1 (coding exon 1) of the TTC30A gene. This alteration results from a G to A substitution at nucleotide position 1925, causing the glycine (G) at amino acid position 642 to be replaced by a glutamic acid (E). 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	0.25
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.24
Sift	Benign	0.18	T
Sift4G	Uncertain	0.041	D
Polyphen		0.19	B
Vest4		0.57
MutPred		0.30		Loss of loop (P = 0.0128);
MVP		0.62
MPC		0.51
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.40
gMVP		0.59

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: rs1359906699; hg19: chr2-178481505;