7-5309170-C-G

Variant names:

• chr7-5309170-C-G
• NM_001080495.3:c.8587G>C

Variant summary

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

The NM_001080495.3(TNRC18):​c.8587G>C​(p.Glu2863Gln) 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: TNRC18 NM_001080495.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

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 rank	MANE	Protein	UniProt
TNRC18	NM_001080495.3	c.8587G>C	p.Glu2863Gln	missense_variant	Exon 28 of 30	ENST00000430969.6	NP_001073964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC18	ENST00000430969.6	c.8587G>C	p.Glu2863Gln	missense_variant	Exon 28 of 30	5	NM_001080495.3	ENSP00000395538.1
TNRC18	ENST00000399537.8	c.8587G>C	p.Glu2863Gln	missense_variant	Exon 28 of 30	5		ENSP00000382452.4

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 specified Uncertain:1

Jun 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8587G>C (p.E2863Q) alteration is located in exon 28 (coding exon 27) of the TNRC18 gene. This alteration results from a G to C substitution at nucleotide position 8587, causing the glutamic acid (E) at amino acid position 2863 to be replaced by a glutamine (Q). 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	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Pathogenic	3.1	.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.78
MutPred		0.41		Gain of MoRF binding (P = 0.0399);Gain of MoRF binding (P = 0.0399);
MVP		0.29
MPC		0.53
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.61
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-5348801;