3-129483544-G-T

Position:

chr3-129483544-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_052989.3(IFT122):c.1713G>T(p.Ser571=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,034 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 32)

Exomes 𝑓: 0.011 ( 152 hom. )

Consequence

IFT122
NM_052989.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.41

Variant links:

Genes affected

IFT122 (HGNC:13556): (intraflagellar transport 122) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This cytoplasmic protein contains seven WD repeats and an AF-2 domain which function by recruiting coregulatory molecules and in transcriptional activation. Mutations in this gene cause cranioectodermal dysplasia-1. A related pseudogene is located on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

IFT122 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 3-129483544-G-T is Benign according to our data. Variant chr3-129483544-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 343243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129483544-G-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.011 (1673/152174) while in subpopulation SAS AF= 0.0294 (141/4800). AF 95% confidence interval is 0.0254. There are 12 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT122	NM_052989.3 linkuse as main transcript	c.1713G>T	p.Ser571=	synonymous_variant	15/30	ENST00000348417.7	NP_443715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7 linkuse as main transcript	c.1713G>T	p.Ser571=	synonymous_variant	15/30	1	NM_052989.3	ENSP00000324005		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1669

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0291

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00868

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0110

AC:

2757

AN:

251444

Hom.:

AF XY:

0.0122

AC XY:

1652

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0324

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00982

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0111

AC:

16179

AN:

1461860

Hom.:

152

Cov.:

AF XY:

0.0117

AC XY:

8481

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.00704

Gnomad4 ASJ exome

AF:

0.00444

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0304

Gnomad4 FIN exome

AF:

0.00241

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0110

AC:

1673

AN:

152174

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

838

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00869

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.0119

EpiCase

AF:

0.00949

EpiControl

AF:

0.0113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cranioectodermal dysplasia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cranioectodermal dysplasia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.012

DANN

Benign

0.66

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