11-118530699-G-T

Position:

• chr11-118530699-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080441.4(TTC36):​c.353G>T​(p.Arg118Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000377 in 1,325,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: TTC36 NM_001080441.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66

Genes affected

TTC36 (HGNC:33708): (tetratricopeptide repeat domain 36) The protein encoded by this gene has three tetratricopeptide repeats and is a chaperone for heat shock protein 70. The encoded protein may function as a tumor suppressor in hepatocellular carcinoma (HCC) since it promotes apoptosis but is downregulated in HCC. [provided by RefSeq, Sep 2016]

TTC36-AS1 (HGNC:55495): (TTC36 and KMT2A antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1952565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC36	NM_001080441.4	c.353G>T	p.Arg118Leu	missense_variant	3/3	ENST00000302783.10	NP_001073910.1
TTC36-AS1	NR_120574.1	n.77C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC36	ENST00000302783.10	c.353G>T	p.Arg118Leu	missense_variant	3/3	1	NM_001080441.4	ENSP00000307640	P1
TTC36-AS1	ENST00000532597.6			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000377 AC: 5 AN: 1325270 Hom.: 0 Cov.: 31 AF XY: 0.00000612 AC XY: 4 AN XY: 653618

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000684

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.353G>T (p.R118L) alteration is located in exon 3 (coding exon 3) of the TTC36 gene. This alteration results from a G to T substitution at nucleotide position 353, causing the arginine (R) at amino acid position 118 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	-0.081
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.18	N
MutationTaster	Benign	0.95	N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Benign	0.24	T
Sift4G	Benign	0.19	T
Polyphen		0.049	B
Vest4		0.22
MutPred		0.50		Loss of methylation at R118 (P = 0.0089);
MVP		0.068
MPC		0.36
ClinPred		0.59	D
GERP RS		4.7
Varity_R		0.32
gMVP		0.42

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118401414;