rs112066509

Variant names:

• chr3-129483473-C-T
• rs112066509
• NM_052989.3:c.1654-12C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-129483473-C-T
• chr3-129483473-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_052989.3(IFT122):​c.1654-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,612,952 control chromosomes in the GnomAD database, including 11,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1589 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10259 hom.)
• Consequence: IFT122 NM_052989.3 intron
• Scores: Splicing: ADA: 0.00003809
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.204
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• cranioectodermal dysplasia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299667 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-129483473-C-T is Benign according to our data. Variant chr3-129483473-C-T is described in ClinVar as Benign. ClinVar VariationId is 262268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052989.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	NM_052989.3	MANE Select	c.1654-12C>T		intron	N/A	NP_443715.1	Q9HBG6-1
	IFT122	NM_052985.4		c.1807-12C>T		intron	N/A	NP_443711.2	Q9HBG6-5
	IFT122	NM_001410808.1		c.1654-12C>T		intron	N/A	NP_001397737.1	A0A8I5KSG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT122	ENST00000348417.7	TSL:1 MANE Select	c.1654-12C>T		intron	N/A	ENSP00000324005.4	Q9HBG6-1
	IFT122	ENST00000296266.7	TSL:1	c.1807-12C>T		intron	N/A	ENSP00000296266.3	Q9HBG6-5
	IFT122	ENST00000507564.5	TSL:1	c.1630-12C>T		intron	N/A	ENSP00000425536.1	Q9HBG6-6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19510 AN: 151760 Hom.: 1584 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0813

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0396

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.116 AC: 28937 AN: 250330 AF XY: 0.123

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.0699

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.0769

Gnomad FIN exome AF: 0.0387

Gnomad NFE exome AF: 0.0956

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.108 AC: 157618 AN: 1461074 Hom.: 10259 Cov.: 32 AF XY: 0.112 AC XY: 81773 AN XY: 726888

African (AFR) AF: 0.216 AC: 7235 AN: 33450

American (AMR) AF: 0.0730 AC: 3265 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4371 AN: 26122

East Asian (EAS) AF: 0.0645 AC: 2558 AN: 39688

South Asian (SAS) AF: 0.248 AC: 21415 AN: 86230

European-Finnish (FIN) AF: 0.0410 AC: 2189 AN: 53420

Middle Eastern (MID) AF: 0.161 AC: 928 AN: 5768

European-Non Finnish (NFE) AF: 0.0975 AC: 108355 AN: 1111302

Other (OTH) AF: 0.121 AC: 7302 AN: 60372

GnomAD4 genome AF: 0.129 AC: 19535 AN: 151878 Hom.: 1589 Cov.: 32 AF XY: 0.128 AC XY: 9515 AN XY: 74230

African (AFR) AF: 0.207 AC: 8582 AN: 41396

American (AMR) AF: 0.104 AC: 1581 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3462

East Asian (EAS) AF: 0.0807 AC: 417 AN: 5168

South Asian (SAS) AF: 0.240 AC: 1142 AN: 4760

European-Finnish (FIN) AF: 0.0396 AC: 419 AN: 10570

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0942 AC: 6400 AN: 67948

Other (OTH) AF: 0.139 AC: 292 AN: 2102

Alfa AF: 0.0793 Hom.: 167

Bravo AF: 0.135

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cranioectodermal dysplasia 1 (2)
-	-	2	not specified (2)
-	-	1	Cranioectodermal dysplasia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.37
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs112066509; hg19: chr3-129202316; COSMIC: COSV56208786; COSMIC: COSV56208786;