3-160375890-G-T

Variant names:

• chr3-160375890-G-T
• rs188321058
• NM_020800.3:c.371-10C>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020800.3(IFT80):​c.371-10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,558,710 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (32 hom.)
• Consequence: IFT80 NM_020800.3 intron
• Scores: Splicing: ADA: 0.01914
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.110

Genes affected

IFT80 (HGNC:29262): (intraflagellar transport 80) The protein encoded by this gene is part of the intraflagellar transport complex B and is necessary for the function of motile and sensory cilia. Defects in this gene are a cause of asphyxiating thoracic dystrophy 2 (ATD2). Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

ENSG00000248710 (HGNC:56756): (TRIM59-IFT80 readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring TRIM59 (tripartite motif containing 59) and IFT80 (intraflagellar transport 80) genes on chromosome 3. The readthrough transcript is unlikely to produce a protein product. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 3-160375890-G-T is Benign according to our data. Variant chr3-160375890-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 284855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-160375890-G-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00422 (634/150126) while in subpopulation NFE AF= 0.00634 (427/67354). AF 95% confidence interval is 0.00584. There are 3 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT80	NM_020800.3	c.371-10C>A		intron_variant	Intron 4 of 19	ENST00000326448.12	NP_065851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT80	ENST00000326448.12	c.371-10C>A		intron_variant	Intron 4 of 19	1	NM_020800.3	ENSP00000312778.7
ENSG00000248710	ENST00000483754.1	n.953-9738C>A		intron_variant	Intron 3 of 18	2		ENSP00000456272.1

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 634 AN: 150022 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00292

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00549

Gnomad FIN AF: 0.00715

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00634

Gnomad OTH AF: 0.00390

GnomAD3 exomes AF: 0.00436 AC: 972 AN: 222694 Hom.: 5 AF XY: 0.00473 AC XY: 571 AN XY: 120682

Gnomad AFR exome AF: 0.000716

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00424

Gnomad FIN exome AF: 0.00627

Gnomad NFE exome AF: 0.00602

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00561 AC: 7900 AN: 1408584 Hom.: 32 Cov.: 25 AF XY: 0.00567 AC XY: 3988 AN XY: 702846

Gnomad4 AFR exome AF: 0.000968

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00439

Gnomad4 FIN exome AF: 0.00544

Gnomad4 NFE exome AF: 0.00638

Gnomad4 OTH exome AF: 0.00447

GnomAD4 genome AF: 0.00422 AC: 634 AN: 150126 Hom.: 3 Cov.: 32 AF XY: 0.00446 AC XY: 327 AN XY: 73280

Gnomad4 AFR AF: 0.00129

Gnomad4 AMR AF: 0.00292

Gnomad4 ASJ AF: 0.00116

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00550

Gnomad4 FIN AF: 0.00715

Gnomad4 NFE AF: 0.00634

Gnomad4 OTH AF: 0.00386

Alfa AF: 0.00470 Hom.: 0

Bravo AF: 0.00350

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Asphyxiating thoracic dystrophy 2 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Oct 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IFT80: BS2 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Dec 07, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jeune thoracic dystrophy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder Benign:1

Jan 21, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.019
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs188321058; hg19: chr3-160093678;