2-177617100-A-T

Position:

• chr2-177617100-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152275.4(IFT70A):​c.1602T>A​(p.Asp534Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,460,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: IFT70A NM_152275.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.360

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01703611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT70A	NM_152275.4	c.1602T>A	p.Asp534Glu	missense_variant	1/1	ENST00000355689.6	NP_689488.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT70A	ENST00000355689.6	c.1602T>A	p.Asp534Glu	missense_variant	1/1		NM_152275.4	ENSP00000347915	P1
	ENST00000357045.4	n.86-201A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1460220 Hom.: 0 Cov.: 39 AF XY: 0.0000289 AC XY: 21 AN XY: 726364

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: 0.0000369

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 25

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

Dec 06, 2023

The c.1602T>A (p.D534E) alteration is located in exon 1 (coding exon 1) of the TTC30A gene. This alteration results from a T to A substitution at nucleotide position 1602, causing the aspartic acid (D) at amino acid position 534 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	0.082
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.25
DANN	Benign	0.52
DEOGEN2	Benign	0.00016	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	0.92	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.17		Gain of ubiquitination at K539 (P = 0.115);
MVP		0.34
MPC		0.31
ClinPred		0.069	T
GERP RS		-9.8
Varity_R		0.022
gMVP		0.22

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: chr2-178481828;