rs140567902

Variant names:

• chr9-15185332-C-T
• rs140567902
• NM_152574.3:c.1364G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-15185332-C-T
• chr9-15185332-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152574.3(TTC39B):​c.1364G>A​(p.Arg455Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: TTC39B NM_152574.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3228535).

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.1364G>A	p.Arg455Gln	missense	Exon 16 of 20	NP_689787.3	A0A8V8PNE1
	TTC39B	NM_001168339.2		c.1358G>A	p.Arg453Gln	missense	Exon 16 of 20	NP_001161811.2
	TTC39B	NM_001168340.2		c.1325G>A	p.Arg442Gln	missense	Exon 15 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.1364G>A	p.Arg455Gln	missense	Exon 16 of 20	ENSP00000422496.2	A0A8V8PNE1
	TTC39B	ENST00000380853.1	TSL:1	n.384G>A		non_coding_transcript_exon	Exon 3 of 7
	TTC39B	ENST00000380850.9	TSL:2	c.1325G>A	p.Arg442Gln	missense	Exon 15 of 19	ENSP00000370231.5	A0A8V8NCV2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251162 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1461546 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111794

Other (OTH) AF: 0.0000331 AC: 2 AN: 60380

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.11
Sift	Benign	0.42	T
Sift4G	Benign	0.35	T
Vest4		0.36
MVP		0.22
MPC		0.15
ClinPred		0.46	T
GERP RS		5.8
Varity_R		0.13
gMVP		0.42
Mutation Taster		=82/18	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: rs140567902; hg19: chr9-15185330;