Variant 11-118555251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001168618.2(IFT46):c.257G>A(p.Ser86Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

IFT46
NM_001168618.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

IFT46 (HGNC:26146): (intraflagellar transport 46) Predicted to enable protein C-terminus binding activity. Predicted to be involved in cilium assembly; intraciliary transport; and protein stabilization. Predicted to act upstream of or within smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFT46 links:

IFT46 (HGNC:):

IFT46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.035196513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT46	NM_001168618.2 linkuse as main transcript	c.257G>A	p.Ser86Asn	missense_variant	5/12	ENST00000264021.8	NP_001162089.1	Q9NQC8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT46	ENST00000264021.8 linkuse as main transcript	c.257G>A	p.Ser86Asn	missense_variant	5/12	1	NM_001168618.2	ENSP00000264021.3		Q9NQC8-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

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

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251442

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000554

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:

0.00000274

AC:

AN:

1459202

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726022

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

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

AF:

0.000131

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000481

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

Alfa

AF:

0.0000591

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Dec 21, 2022

The c.410G>A (p.S137N) alteration is located in exon 6 (coding exon 4) of the IFT46 gene. This alteration results from a G to A substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0036

T;.;.;.;.;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0040

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.78

T;T;T;T;T;T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.035

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.;.;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.56

N;N;N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.27

T;T;T;T;T;D;T

Sift4G

Benign

0.38

T;T;T;.;.;T;.

Polyphen

0.35

B;B;B;.;.;.;.

Vest4

0.12

MVP

0.093

MPC

0.19

ClinPred

0.035

GERP RS

3.8

Varity_R

0.082

gMVP

0.12

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