rs61743977

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_015662.3(IFT172):c.1685C>G(p.Thr562Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,603,214 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 55 hom. )

Consequence

IFT172
NM_015662.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 9.14

Variant links:

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

IFT172 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-27470935-G-C is Benign according to our data. Variant chr2-27470935-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 476042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-27470935-G-C is described in Lovd as [Benign]. Variant chr2-27470935-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00488 (743/152240) while in subpopulation NFE AF= 0.00701 (477/68018). AF 95% confidence interval is 0.00649. There are 4 homozygotes in gnomad4. There are 362 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT172	NM_015662.3 link	c.1685C>G	p.Thr562Ser	missense_variant	Exon 16 of 48	ENST00000260570.8	NP_056477.1	Q9UG01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT172	ENST00000260570.8 link	c.1685C>G	p.Thr562Ser	missense_variant	Exon 16 of 48	1	NM_015662.3	ENSP00000260570.3		Q9UG01-1

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

742

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00701

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00650

AC:

1565

AN:

240620

Hom.:

AF XY:

0.00686

AC XY:

894

AN XY:

130328

show subpopulations

Gnomad AFR exome

AF:

0.000997

Gnomad AMR exome

AF:

0.00407

Gnomad ASJ exome

AF:

0.0217

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00753

Gnomad FIN exome

AF:

0.00295

Gnomad NFE exome

AF:

0.00801

Gnomad OTH exome

AF:

0.00921

GnomAD4 exome

AF:

0.00617

AC:

8948

AN:

1450974

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

4590

AN XY:

721596

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.0219

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00818

Gnomad4 FIN exome

AF:

0.00321

Gnomad4 NFE exome

AF:

0.00597

Gnomad4 OTH exome

AF:

0.00785

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152240

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

362

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00701

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.00502

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00651

AC:

ExAC

AF:

0.00698

AC:

847

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 15, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 30, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IFT172: BP4, BS2 -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.11

Eigen

Benign

-0.19

Eigen_PC

Benign

0.065

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.33

PROVEAN

Benign

0.26

REVEL

Benign

0.16

Sift

Benign

0.39

Sift4G

Benign

0.14

Polyphen

0.0020

Vest4

0.093

MutPred

0.41

Loss of sheet (P = 0.0817);

MVP

0.11

MPC

0.16

ClinPred

0.048

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.075

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: -7

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