3-160375890-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 Benign/Likely_benign. ClinVar VariationId is 284855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	NM_020800.3	MANE Select	c.371-10C>A		intron	N/A	NP_065851.1
	IFT80	NM_001190241.2		c.-41-10C>A		intron	N/A	NP_001177170.1
	IFT80	NM_001190242.2		c.-41-10C>A		intron	N/A	NP_001177171.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT80	ENST00000326448.12	TSL:1 MANE Select	c.371-10C>A		intron	N/A	ENSP00000312778.7
	IFT80	ENST00000483465.5	TSL:1	c.-41-10C>A		intron	N/A	ENSP00000418196.1
	TRIM59-IFT80	ENST00000483754.1	TSL:2	n.953-9738C>A		intron	N/A	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

GnomAD2 exomes AF: 0.00436 AC: 972 AN: 222694 AF XY: 0.00473

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 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

African (AFR) AF: 0.000968 AC: 31 AN: 32024

American (AMR) AF: 0.00244 AC: 106 AN: 43402

Ashkenazi Jewish (ASJ) AF: 0.00106 AC: 27 AN: 25474

East Asian (EAS) AF: 0.00 AC: 0 AN: 38786

South Asian (SAS) AF: 0.00439 AC: 366 AN: 83430

European-Finnish (FIN) AF: 0.00544 AC: 288 AN: 52928

Middle Eastern (MID) AF: 0.00126 AC: 7 AN: 5554

European-Non Finnish (NFE) AF: 0.00638 AC: 6815 AN: 1068762

Other (OTH) AF: 0.00447 AC: 260 AN: 58224

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

African (AFR) AF: 0.00129 AC: 53 AN: 41040

American (AMR) AF: 0.00292 AC: 44 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00550 AC: 26 AN: 4724

European-Finnish (FIN) AF: 0.00715 AC: 72 AN: 10064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00634 AC: 427 AN: 67354

Other (OTH) AF: 0.00386 AC: 8 AN: 2074

Alfa AF: 0.00438 Hom.: 0

Bravo AF: 0.00350

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.79
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs188321058; hg19: chr3-160093678;