chr9-15246654-C-T

Variant names:

• chr9-15246654-C-T
• rs519664
• NM_152574.3:c.78-20642G>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.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
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152574.3. 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
	TTC39B	NM_152574.3	MANE Select	c.78-20642G>A		intron	N/A	NP_689787.3
	TTC39B	NM_001168339.2		c.78-20642G>A		intron	N/A	NP_001161811.2
	TTC39B	NM_001168340.2		c.78-20642G>A		intron	N/A	NP_001161812.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC39B	ENST00000512701.7	TSL:2 MANE Select	c.78-20642G>A		intron	N/A	ENSP00000422496.2
	TTC39B	ENST00000505732.5	TSL:1	n.313-20642G>A		intron	N/A
	TTC39B	ENST00000380850.9	TSL:2	c.78-20642G>A		intron	N/A	ENSP00000370231.5

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

African (AFR) AF: 0.745 AC: 30943 AN: 41508

American (AMR) AF: 0.246 AC: 3763 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3468

East Asian (EAS) AF: 0.142 AC: 732 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2395 AN: 10588

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14712 AN: 67986

Other (OTH) AF: 0.315 AC: 665 AN: 2112

Alfa AF: 0.253 Hom.: 11332

Bravo AF: 0.380

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.50
PhyloP100		-0.64
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: rs519664; hg19: chr9-15246652; COSMIC: COSV52615468; COSMIC: COSV52615468;