chr9-15177789-A-T

Position:

• chr9-15177789-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152574.3(TTC39B):​c.1551T>A​(p.Asp517Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC39B NM_152574.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.60

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]

TTC39B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC39B	NM_152574.3	c.1551T>A	p.Asp517Glu	missense_variant	18/20	ENST00000512701.7	NP_689787.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC39B	ENST00000512701.7	c.1551T>A	p.Asp517Glu	missense_variant	18/20	2	NM_152574.3	ENSP00000422496.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.1749T>A (p.D583E) alteration is located in exon 18 (coding exon 18) of the TTC39B gene. This alteration results from a T to A substitution at nucleotide position 1749, causing the aspartic acid (D) at amino acid position 583 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	7.3
DANN	Benign	0.95
DEOGEN2	Benign	0.20	T;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.046	N
LIST_S2	Uncertain	0.97	D;D;D;.;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Pathogenic	3.2	M;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Benign	0.037	D;D;D;T;T
Sift4G	Uncertain	0.048	D;D;D;T;T
Vest4		0.83
MVP		0.13
MPC		0.28
ClinPred		0.98	D
GERP RS		-12
Varity_R		0.52
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1818024050; hg19: chr9-15177787;