chr11-62738369-G-C

Variant names:

• chr11-62738369-G-C
• rs1337670595
• NM_173810.4:c.503G>C

Variant summary

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

The NM_173810.4(TTC9C):​c.503G>C​(p.Gly168Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC9C NM_173810.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.37
• 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.503G>C	p.Gly168Ala	missense	Exon 3 of 3	NP_776171.1	Q8N5M4-1
	TTC9C	NM_001318812.2		c.503G>C	p.Gly168Ala	missense	Exon 4 of 4	NP_001305741.1	Q8N5M4-1
	TTC9C	NM_001318813.2		c.503G>C	p.Gly168Ala	missense	Exon 4 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.503G>C	p.Gly168Ala	missense	Exon 3 of 3	ENSP00000325266.3	Q8N5M4-1
	TTC9C	ENST00000532583.1	TSL:1	c.503G>C	p.Gly168Ala	missense	Exon 4 of 4	ENSP00000434340.1	Q8N5M4-1
	TTC9C	ENST00000851206.1		c.503G>C	p.Gly168Ala	missense	Exon 4 of 4	ENSP00000521265.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	Benign	0.33
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.70		Loss of stability (P = 0.0506)
MVP		0.89
MPC		0.51
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.41
gMVP		0.32
Mutation Taster		=26/74	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: rs1337670595; hg19: chr11-62505841;