rs12003180

Variant names:

• chr9-15283099-C-T
• rs12003180
• NM_152574.3:c.43-15151G>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.43-15151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 152,128 control chromosomes in the GnomAD database, including 1,034 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 0.090 (1034 hom., cov: 33)
• Consequence: TTC39B NM_152574.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC39B	NM_152574.3	c.43-15151G>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.43-15151G>A		intron_variant	Intron 1 of 19	2	NM_152574.3	ENSP00000422496.2

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13685 AN: 152008 Hom.: 1027 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0902 AC: 13724 AN: 152128 Hom.: 1034 Cov.: 33 AF XY: 0.0873 AC XY: 6494 AN XY: 74374

African (AFR) AF: 0.207 AC: 8563 AN: 41456

American (AMR) AF: 0.0507 AC: 774 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5174

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4818

European-Finnish (FIN) AF: 0.0411 AC: 435 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0491 AC: 3343 AN: 68018

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0665 Hom.: 1013

Bravo AF: 0.0953

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.82
PhyloP100		-3.3
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: rs12003180; hg19: chr9-15283097;