rs519664

chr9-15246654-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152574.3(TTC39B):c.78-20642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,144 control chromosomes in the GnomAD database, including 14,383 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 0.36 (14383 hom., cov: 33)
• Consequence: TTC39B NM_152574.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC39B	NM_152574.3	c.78-20642G>A		intron_variant		ENST00000512701.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39B	ENST00000512701.7	c.78-20642G>A		intron_variant		2	NM_152574.3	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54869 AN: 152026 Hom.: 14331 Cov.: 33

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.361 AC: 54981 AN: 152144 Hom.: 14383 Cov.: 33 AF XY: 0.355 AC XY: 26415 AN XY: 74402

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.315

Alfa AF: 0.240 Hom.: 7190

Bravo AF: 0.380

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.71
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs519664; hg19: chr9-15246652; COSMIC: COSV52615468; COSMIC: COSV52615468;