11-62729037-A-C

Variant names:

• chr11-62729037-A-C
• NM_173810.4:c.189A>C
• TTC9C p.Gln63His

Variant summary

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

The NM_173810.4(TTC9C):​c.189A>C​(p.Gln63His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q63P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC9C NM_173810.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

Genes affected

TTC9C (HGNC:28432): (tetratricopeptide repeat domain 9C)

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_173810.4. 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
	TTC9C	NM_173810.4	MANE Select	c.189A>C	p.Gln63His	missense	Exon 1 of 3	NP_776171.1	Q8N5M4-1
	TTC9C	NM_001318812.2		c.189A>C	p.Gln63His	missense	Exon 2 of 4	NP_001305741.1	Q8N5M4-1
	TTC9C	NM_001318813.2		c.189A>C	p.Gln63His	missense	Exon 2 of 4	NP_001305742.1	Q8N5M4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC9C	ENST00000316461.9	TSL:1 MANE Select	c.189A>C	p.Gln63His	missense	Exon 1 of 3	ENSP00000325266.3	Q8N5M4-1
	TTC9C	ENST00000532583.1	TSL:1	c.189A>C	p.Gln63His	missense	Exon 2 of 4	ENSP00000434340.1	Q8N5M4-1
	TTC9C	ENST00000294161.10	TSL:1	n.189A>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000294161.6	E7EST3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.078	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.031	D
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.47
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-62496509;