chr19-40218189-C-T

Variant names:

• chr19-40218189-C-T
• rs376663858
• NM_152479.6:c.193G>A

Variant summary

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

The NM_152479.6(TTC9B):​c.193G>A​(p.Ala65Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000984 in 1,422,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: TTC9B NM_152479.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02
• Publications: 0 publications found

Genes affected

TTC9B (HGNC:26395): (tetratricopeptide repeat domain 9B)

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_152479.6. 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
	TTC9B	NM_152479.6	MANE Select	c.193G>A	p.Ala65Thr	missense	Exon 1 of 3	NP_689692.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC9B	ENST00000311308.7	TSL:1 MANE Select	c.193G>A	p.Ala65Thr	missense	Exon 1 of 3	ENSP00000311760.6	Q8N6N2-1
	TTC9B	ENST00000959521.1		c.193G>A	p.Ala65Thr	missense	Exon 1 of 3	ENSP00000629580.1
	TTC9B	ENST00000854610.1		c.193G>A	p.Ala65Thr	missense	Exon 1 of 3	ENSP00000524669.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000984 AC: 14 AN: 1422910 Hom.: 0 Cov.: 35 AF XY: 0.00000989 AC XY: 7 AN XY: 707624

African (AFR) AF: 0.00 AC: 0 AN: 29294

American (AMR) AF: 0.00 AC: 0 AN: 39950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24906

East Asian (EAS) AF: 0.00 AC: 0 AN: 34062

South Asian (SAS) AF: 0.00 AC: 0 AN: 82376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5152

European-Non Finnish (NFE) AF: 0.0000128 AC: 14 AN: 1096836

Other (OTH) AF: 0.00 AC: 0 AN: 58648

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.57
MVP		0.55
MPC		1.9
ClinPred		1.0	D
GERP RS		4.5
PromoterAI		0.0062	Neutral
Varity_R		0.65
gMVP		0.76
Mutation Taster		=56/44	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: rs376663858; hg19: chr19-40724096;