NM_152574.3:c.1711A>G

Variant names:

• chr9-15175068-T-C
• rs1817858513
• NM_152574.3:c.1711A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152574.3(TTC39B):​c.1711A>G​(p.Lys571Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K571N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC39B NM_152574.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC39B	NM_152574.3	MANE Select	c.1711A>G	p.Lys571Glu	missense	Exon 19 of 20	NP_689787.3	A0A8V8PNE1
	TTC39B	NM_001168339.2		c.1705A>G	p.Lys569Glu	missense	Exon 19 of 20	NP_001161811.2
	TTC39B	NM_001168340.2		c.1672A>G	p.Lys558Glu	missense	Exon 18 of 19	NP_001161812.2	A0A8V8NCV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC39B	ENST00000512701.7	TSL:2 MANE Select	c.1711A>G	p.Lys571Glu	missense	Exon 19 of 20	ENSP00000422496.2	A0A8V8PNE1
	TTC39B	ENST00000380853.1	TSL:1	n.731A>G		non_coding_transcript_exon	Exon 6 of 7
	TTC39B	ENST00000380850.9	TSL:2	c.1672A>G	p.Lys558Glu	missense	Exon 18 of 19	ENSP00000370231.5	A0A8V8NCV2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.1
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.19
Sift	Benign	0.27	T
Sift4G	Benign	0.27	T
Vest4		0.72
MVP		0.56
MPC		0.28
ClinPred		0.82	D
GERP RS		3.2
Varity_R		0.21
gMVP		0.63
Mutation Taster		=64/36	polymorphism

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: rs1817858513; hg19: chr9-15175066;