7-5308921-A-C

Position:

• chr7-5308921-A-C

Variant summary

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

The NM_001080495.3(TNRC18):​c.8654T>G​(p.Leu2885Arg) variant causes a missense change. 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: TNRC18 NM_001080495.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47

Genes affected

TNRC18 (HGNC:11962): (trinucleotide repeat containing 18) Predicted to enable chromatin binding activity. Located in cytosol; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC18	NM_001080495.3	c.8654T>G	p.Leu2885Arg	missense_variant	29/30	ENST00000430969.6	NP_001073964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC18	ENST00000430969.6	c.8654T>G	p.Leu2885Arg	missense_variant	29/30	5	NM_001080495.3	ENSP00000395538.1
TNRC18	ENST00000399537.8	c.8654T>G	p.Leu2885Arg	missense_variant	29/30	5		ENSP00000382452.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

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

Dec 05, 2022

The c.8654T>G (p.L2885R) alteration is located in exon 29 (coding exon 28) of the TNRC18 gene. This alteration results from a T to G substitution at nucleotide position 8654, causing the leucine (L) at amino acid position 2885 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Benign	-0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.99	.;D
Vest4		0.81
MutPred		0.27		Gain of methylation at L2885 (P = 0.0248);Gain of methylation at L2885 (P = 0.0248);
MVP		0.10
MPC		0.79
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.41
gMVP		0.89

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: chr7-5348552;