Variant 2-177617660-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152275.4(IFT70A):c.1042C>T(p.His348Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IFT70A
NM_152275.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.57

Variant links:

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]

IFT70A links:

ENSG00000237655 (HGNC:):

ENSG00000237655 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1042C>T	p.His348Tyr	missense_variant	1/1	ENST00000355689.6	NP_689488.3	Q86WT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC30A	ENST00000355689.6 linkuse as main transcript	c.1042C>T	p.His348Tyr	missense_variant	1/1	6	NM_152275.4	ENSP00000347915.4		Q86WT1
ENSG00000237655	ENST00000357045.4 linkuse as main transcript	n.305+140G>A		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251058

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.1042C>T (p.H348Y) alteration is located in exon 1 (coding exon 1) of the TTC30A gene. This alteration results from a C to T substitution at nucleotide position 1042, causing the histidine (H) at amino acid position 348 to be replaced by a tyrosine (Y). 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

0.21

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.9

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.013

Polyphen

0.99

Vest4

0.38

MutPred

0.50

Gain of helix (P = 0.0861);

MVP

0.72

MPC

0.98

ClinPred

0.88

GERP RS

5.9

Varity_R

0.38

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over