rs72700653

Positions:

• chr9-15249052-T-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.*680A>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 0.0415 in 152,296 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (162 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TTC39B ENST00000506891.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.724

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=-0.83).
• BP6: Variant 9-15249052-T-C is Benign according to our data. Variant chr9-15249052-T-C is described in ClinVar as [Benign]. Clinvar id is 1244123.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	Protein	UniProt
TTC39B	NM_152574.3	c.77+18862A>G		intron_variant		ENST00000512701.7	NP_689787.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39B	ENST00000512701.7	c.77+18862A>G		intron_variant		2	NM_152574.3	ENSP00000422496	P1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6301 AN: 152178 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0435

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0415 AC: 6313 AN: 152296 Hom.: 162 Cov.: 32 AF XY: 0.0435 AC XY: 3238 AN XY: 74458

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0254

Gnomad4 OTH AF: 0.0425

Alfa AF: 0.0282 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	-0.83
CADD	Benign	4.3
DANN	Benign	0.70

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: rs72700653; hg19: chr9-15249050;