3-160366130-C-T

Variant names:

• chr3-160366130-C-T
• rs34182424
• NM_020800.3:c.462G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020800.3(IFT80):​c.462G>A​(p.Ala154Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,610,788 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A154A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.023 (58 hom., cov: 32)
  • Exomes 𝑓: 0.019 (346 hom.)
• Consequence: IFT80 NM_020800.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.08
• Publications: 3 publications found

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]

TRIM59-IFT80 (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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-160366130-C-T is Benign according to our data. Variant chr3-160366130-C-T is described in ClinVar as Benign. ClinVar VariationId is 343980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.08 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0229 (3457/151018) while in subpopulation AFR AF = 0.0363 (1492/41114). AF 95% confidence interval is 0.0348. There are 58 homozygotes in GnomAd4. There are 1652 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020800.3. 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
	IFT80	NM_020800.3	MANE Select	c.462G>A	p.Ala154Ala	synonymous	Exon 6 of 20	NP_065851.1	Q9P2H3-1
	IFT80	NM_001190241.2		c.51G>A	p.Ala17Ala	synonymous	Exon 7 of 21	NP_001177170.1	Q9P2H3-2
	IFT80	NM_001190242.2		c.51G>A	p.Ala17Ala	synonymous	Exon 5 of 19	NP_001177171.1	Q9P2H3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	ENST00000326448.12	TSL:1 MANE Select	c.462G>A	p.Ala154Ala	synonymous	Exon 6 of 20	ENSP00000312778.7	Q9P2H3-1
	IFT80	ENST00000483465.5	TSL:1	c.51G>A	p.Ala17Ala	synonymous	Exon 5 of 19	ENSP00000418196.1	Q9P2H3-2
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.975G>A		non_coding_transcript_exon	Exon 4 of 19	ENSP00000456272.1	H3BRJ5

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3452 AN: 150902 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00501

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0214

GnomAD2 exomes AF: 0.0165 AC: 4149 AN: 250950 AF XY: 0.0161

Gnomad AFR exome AF: 0.0403

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.0389

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00481

Gnomad NFE exome AF: 0.0203

Gnomad OTH exome AF: 0.0207

GnomAD4 exome AF: 0.0191 AC: 27847 AN: 1459770 Hom.: 346 Cov.: 31 AF XY: 0.0189 AC XY: 13710 AN XY: 726280

African (AFR) AF: 0.0372 AC: 1241 AN: 33400

American (AMR) AF: 0.0121 AC: 542 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0365 AC: 951 AN: 26070

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39656

South Asian (SAS) AF: 0.00713 AC: 615 AN: 86206

European-Finnish (FIN) AF: 0.00564 AC: 301 AN: 53400

Middle Eastern (MID) AF: 0.0456 AC: 259 AN: 5678

European-Non Finnish (NFE) AF: 0.0205 AC: 22752 AN: 1110372

Other (OTH) AF: 0.0196 AC: 1182 AN: 60296

GnomAD4 genome AF: 0.0229 AC: 3457 AN: 151018 Hom.: 58 Cov.: 32 AF XY: 0.0224 AC XY: 1652 AN XY: 73696

African (AFR) AF: 0.0363 AC: 1492 AN: 41114

American (AMR) AF: 0.0228 AC: 344 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.00543 AC: 26 AN: 4788

European-Finnish (FIN) AF: 0.00367 AC: 38 AN: 10364

Middle Eastern (MID) AF: 0.0207 AC: 6 AN: 290

European-Non Finnish (NFE) AF: 0.0203 AC: 1376 AN: 67770

Other (OTH) AF: 0.0212 AC: 44 AN: 2078

Alfa AF: 0.0226 Hom.: 62

Bravo AF: 0.0258

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0223

EpiControl AF: 0.0214

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Asphyxiating thoracic dystrophy 2 (2)
-	-	1	Connective tissue disorder (1)
-	-	1	Jeune thoracic dystrophy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs34182424; hg19: chr3-160083918; COSMIC: COSV58451288;