NM_018010.4:c.1232A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018010.4(IFT57):c.1232A>G(p.Asn411Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,612,394 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 128 hom. )

Consequence

IFT57
NM_018010.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.39

Variant links:

Genes affected

IFT57 (HGNC:17367): (intraflagellar transport 57) Predicted to enable DNA binding activity. Acts upstream of or within activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptotic process; and regulation of apoptotic process. Predicted to be located in ciliary basal body. Predicted to be part of axoneme and intraciliary transport particle B. Predicted to be active in Golgi apparatus; centrosome; and cilium. Implicated in orofaciodigital syndrome. [provided by Alliance of Genome Resources, Apr 2022]

IFT57 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008654356).

BP6

Variant 3-108162535-T-C is Benign according to our data. Variant chr3-108162535-T-C is described in ClinVar as [Benign]. Clinvar id is 774602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0122 (17837/1460060) while in subpopulation MID AF= 0.029 (167/5760). AF 95% confidence interval is 0.0254. There are 128 homozygotes in gnomad4_exome. There are 8935 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT57	NM_018010.4 link	c.1232A>G	p.Asn411Ser	missense_variant	Exon 11 of 11	ENST00000264538.4	NP_060480.1	Q9NWB7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT57	ENST00000264538.4 link	c.1232A>G	p.Asn411Ser	missense_variant	Exon 11 of 11	1	NM_018010.4	ENSP00000264538.3		Q9NWB7

Frequencies

GnomAD3 genomes

AF:

0.00897

AC:

1366

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0101

AC:

2533

AN:

250672

Hom.:

AF XY:

0.0108

AC XY:

1461

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.00930

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00845

Gnomad FIN exome

AF:

0.00883

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.0122

AC:

17837

AN:

1460060

Hom.:

128

Cov.:

AF XY:

0.0123

AC XY:

8935

AN XY:

726330

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.00909

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00887

Gnomad4 FIN exome

AF:

0.00819

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.00895

AC:

1364

AN:

152334

Hom.:

Cov.:

AF XY:

0.00843

AC XY:

628

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.00937

TwinsUK

AF:

0.0189

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0143

AC:

123

ExAC

AF:

0.00981

AC:

1191

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

IFT57-related disorder

Benign:1

Mar 27, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0087

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

REVEL

Benign

0.24

Sift

Benign

0.087

Sift4G

Benign

0.35

Polyphen

0.94

Vest4

0.66

MPC

0.20

ClinPred

0.064

GERP RS

5.9

Varity_R

0.14

gMVP

0.068

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