chr19-40218113-C-T

Variant names:

• chr19-40218113-C-T
• NM_152479.6:c.269G>A

Variant summary

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

The NM_152479.6(TTC9B):​c.269G>A​(p.Arg90Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC9B NM_152479.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76
• Publications: 0 publications found

Genes affected

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

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=0.39569432).

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.269G>A	p.Arg90Gln	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.269G>A	p.Arg90Gln	missense	Exon 1 of 3	ENSP00000311760.6	Q8N6N2-1
	TTC9B	ENST00000959521.1		c.269G>A	p.Arg90Gln	missense	Exon 1 of 3	ENSP00000629580.1
	TTC9B	ENST00000854610.1		c.269G>A	p.Arg90Gln	missense	Exon 1 of 3	ENSP00000524669.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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	0.95
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.30
Sift	Benign	0.038	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.40		Loss of MoRF binding (P = 0.056)
MVP		0.25
MPC		2.2
ClinPred		0.98	D
GERP RS		4.5
PromoterAI		-0.040	Neutral
Varity_R		0.31
gMVP		0.51
Mutation Taster		=49/51	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

hg19: chr19-40724020;