rs643531

Positions:

• chr9-15296036-C-A
• chr9-15296036-C-G

Variant summary

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

The NM_152574.3(TTC39B):​c.42+11048G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,232 control chromosomes in the GnomAD database, including 60,137 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 0.89 (60137 hom., cov: 32)
• Consequence: TTC39B NM_152574.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC39B	NM_152574.3	c.42+11048G>T		intron_variant		ENST00000512701.7	NP_689787.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39B	ENST00000512701.7	c.42+11048G>T		intron_variant		2	NM_152574.3	ENSP00000422496	P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135128 AN: 152114 Hom.: 60092 Cov.: 32

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.888

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

GnomAD4 genome AF: 0.888 AC: 135232 AN: 152232 Hom.: 60137 Cov.: 32 AF XY: 0.890 AC XY: 66246 AN XY: 74420

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.890

Alfa AF: 0.872 Hom.: 76451

Bravo AF: 0.890

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	-0.83
CADD	Benign	3.4
DANN	Benign	0.57

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: rs643531; hg19: chr9-15296034;