9-15289580-C-T

Variant names:

• chr9-15289580-C-T
• rs471364
• NM_152574.3:c.42+17504G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152574.3(TTC39B):​c.42+17504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,198 control chromosomes in the GnomAD database, including 57,766 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57766 hom., cov: 32)
• Consequence: TTC39B NM_152574.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 61 publications found

Genes affected

TTC39B (HGNC:23704): (tetratricopeptide repeat domain 39B) Predicted to be involved in several processes, including cholesterol homeostasis; negative regulation of cholesterol storage; and regulation of cholesterol efflux. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC39B	NM_152574.3	c.42+17504G>A		intron_variant	Intron 1 of 19	ENST00000512701.7	NP_689787.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC39B	ENST00000512701.7	c.42+17504G>A		intron_variant	Intron 1 of 19	2	NM_152574.3	ENSP00000422496.2

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132287 AN: 152080 Hom.: 57740 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.875

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.870 AC: 132368 AN: 152198 Hom.: 57766 Cov.: 32 AF XY: 0.873 AC XY: 64959 AN XY: 74402

African (AFR) AF: 0.802 AC: 33282 AN: 41498

American (AMR) AF: 0.895 AC: 13691 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2989 AN: 3472

East Asian (EAS) AF: 0.981 AC: 5081 AN: 5180

South Asian (SAS) AF: 0.944 AC: 4544 AN: 4812

European-Finnish (FIN) AF: 0.915 AC: 9698 AN: 10600

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60274 AN: 68032

Other (OTH) AF: 0.877 AC: 1851 AN: 2110

Alfa AF: 0.885 Hom.: 209196

Bravo AF: 0.865

Asia WGS AF: 0.951 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.51
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs471364; hg19: chr9-15289578;