7-5308110-C-T

Variant names:

• chr7-5308110-C-T
• rs755613149
• NM_001080495.3:c.8903G>A

Variant summary

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

The NM_001080495.3(TNRC18):​c.8903G>A​(p.Cys2968Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,397,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TNRC18 NM_001080495.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.24
• Publications: 0 publications found

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

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_001080495.3. 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
	TNRC18	NM_001080495.3	MANE Select	c.8903G>A	p.Cys2968Tyr	missense	Exon 30 of 30	NP_001073964.2	O15417-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC18	ENST00000430969.6	TSL:5 MANE Select	c.8903G>A	p.Cys2968Tyr	missense	Exon 30 of 30	ENSP00000395538.1	O15417-1
	TNRC18	ENST00000399537.8	TSL:5	c.8903G>A	p.Cys2968Tyr	missense	Exon 30 of 30	ENSP00000382452.4	H9KVB4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 156854 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000329

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 23 AN: 1397520 Hom.: 0 Cov.: 30 AF XY: 0.0000116 AC XY: 8 AN XY: 689336

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.0000559 AC: 2 AN: 35802

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4068

European-Non Finnish (NFE) AF: 0.0000195 AC: 21 AN: 1079116

Other (OTH) AF: 0.00 AC: 0 AN: 57832

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-9.9	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.53		Gain of solvent accessibility (P = 0.0018)
MVP		0.22
MPC		0.91
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.94
gMVP		0.99
Mutation Taster		=63/37	polymorphism

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: rs755613149; hg19: chr7-5347741;