rs7874043

chr9-15249433-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000506891.1(TTC39B):c.*299T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 152,860 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (159 hom., cov: 32)
  • Exomes 𝑓: 0.017 (0 hom.)
• Consequence: TTC39B ENST00000506891.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.890

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-15249433-A-C is Benign according to our data. Variant chr9-15249433-A-C is described in ClinVar as [Benign]. Clinvar id is 1225250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC39B	NM_152574.3	c.77+18481T>G		intron_variant		ENST00000512701.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC39B	ENST00000512701.7	c.77+18481T>G		intron_variant		2	NM_152574.3	P1

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6290 AN: 152152 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0624

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0170 AC: 10 AN: 588 Hom.: 0 Cov.: 0 AF XY: 0.0102 AC XY: 4 AN XY: 392

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0414 AC: 6302 AN: 152272 Hom.: 159 Cov.: 32 AF XY: 0.0434 AC XY: 3232 AN XY: 74452

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0621

Gnomad4 SAS AF: 0.0469

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0254

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0319 Hom.: 17

Bravo AF: 0.0406

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 26, 2021

This variant is associated with the following publications: (PMID: 26840454) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	11
Dann	Benign	0.88

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: rs7874043; hg19: chr9-15249431;