NM_014714.4:c.*430G>A

Variant names:

• chr16-1510514-C-T
• rs532233762
• NM_014714.4:c.*430G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014714.4(IFT140):​c.*430G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 244,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: IFT140 NM_014714.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.13
• Publications: 0 publications found

Genes affected

IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

TELO2 (HGNC:29099): (telomere maintenance 2) This gene encodes a protein that functions as an S-phase checkpoint protein in the cell cycle. The protein may also play a role in DNA repair.[provided by RefSeq, Mar 2009]

TELO2 Gene-Disease associations (from GenCC):

• TELO2-related intellectual disability-neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014714.4. 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
	IFT140	NM_014714.4	MANE Select	c.*430G>A		3_prime_UTR	Exon 31 of 31	NP_055529.2
	TELO2	NM_016111.4	MANE Select	c.*578C>T		downstream_gene	N/A	NP_057195.2	Q9Y4R8
	TELO2	NM_001351846.2		c.*578C>T		downstream_gene	N/A	NP_001338775.1	Q9Y4R8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT140	ENST00000426508.7	TSL:5 MANE Select	c.*430G>A		3_prime_UTR	Exon 31 of 31	ENSP00000406012.2	Q96RY7-1
	IFT140	ENST00000361339.9	TSL:1	c.*430G>A		3_prime_UTR	Exon 13 of 13	ENSP00000354895.5	Q96RY7-2
	IFT140	ENST00000889170.1		c.*430G>A		3_prime_UTR	Exon 30 of 30	ENSP00000559229.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000324 AC: 3 AN: 92526 Hom.: 0 Cov.: 0 AF XY: 0.0000407 AC XY: 2 AN XY: 49090

African (AFR) AF: 0.00 AC: 0 AN: 1556

American (AMR) AF: 0.00 AC: 0 AN: 4052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2398

East Asian (EAS) AF: 0.00 AC: 0 AN: 2560

South Asian (SAS) AF: 0.00 AC: 0 AN: 14828

European-Finnish (FIN) AF: 0.000645 AC: 3 AN: 4648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57070

Other (OTH) AF: 0.00 AC: 0 AN: 5012

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74452

African (AFR) AF: 0.000193 AC: 8 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67996

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000869

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Saldino-Mainzer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-1.1

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

Other links and lift over

dbSNP: rs532233762; hg19: chr16-1560515;