17-78049307-G-A

Variant summary

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

The NM_001142640.2(TNRC6C):c.875G>A(p.Arg292Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNRC6C NM_001142640.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46

Genes affected

TNRC6C (HGNC:29318): (trinucleotide repeat containing adaptor 6C) Predicted to enable RNA binding activity. Involved in gene silencing by miRNA; positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; and positive regulation of nuclear-transcribed mRNA poly(A) tail shortening. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2370016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6C	NM_001142640.2	c.875G>A	p.Arg292Lys	missense_variant	5/23	ENST00000696270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6C	ENST00000696270.1	c.875G>A	p.Arg292Lys	missense_variant	5/23		NM_001142640.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

TNRC6C: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.013	T;.;T;T;.;.
Eigen	Benign	0.046
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;.;D;D;D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.85	D;D;D;D;D;D
PrimateAI	Benign	0.44	T
Polyphen		0.25, 0.16	.;B;B;B;B;.
Vest4		0.47, 0.46, 0.53, 0.47
MutPred		0.33		.;Gain of ubiquitination at R82 (P = 0.0121);Gain of ubiquitination at R82 (P = 0.0121);Gain of ubiquitination at R82 (P = 0.0121);Gain of ubiquitination at R82 (P = 0.0121);Gain of ubiquitination at R82 (P = 0.0121);
MVP		0.17
MPC		0.50
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.18
gMVP		0.41

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: chr17-76045388; COSMIC: COSV100050063; COSMIC: COSV100050063;