rs997396622

Variant names:

• chr9-15185368-G-A
• rs997396622
• NM_152574.3:c.1328C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-15185368-G-A
• chr9-15185368-G-C
• chr9-15185368-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152574.3(TTC39B):​c.1328C>T​(p.Ser443Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S443C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TTC39B NM_152574.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.85
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

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.1328C>T	p.Ser443Phe	missense	Exon 16 of 20	NP_689787.3	A0A8V8PNE1
	TTC39B	NM_001168339.2		c.1322C>T	p.Ser441Phe	missense	Exon 16 of 20	NP_001161811.2
	TTC39B	NM_001168340.2		c.1289C>T	p.Ser430Phe	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.1328C>T	p.Ser443Phe	missense	Exon 16 of 20	ENSP00000422496.2	A0A8V8PNE1
	TTC39B	ENST00000380853.1	TSL:1	n.348C>T		non_coding_transcript_exon	Exon 3 of 7
	TTC39B	ENST00000380850.9	TSL:2	c.1289C>T	p.Ser430Phe	missense	Exon 15 of 19	ENSP00000370231.5	A0A8V8NCV2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461534 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727088

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111770

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		9.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.026	D
Sift4G	Pathogenic	0.0	D
Vest4		0.93
MVP		0.67
MPC		0.33
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.66
gMVP		0.61
Mutation Taster		=22/78	disease causing

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: rs997396622; hg19: chr9-15185366; COSMIC: COSV52616555; COSMIC: COSV52616555;