rs370539555

Variant names:

• chr7-5308196-C-A
• rs370539555
• NM_001080495.3:c.8817G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-5308196-C-A
• chr7-5308196-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080495.3(TNRC18):​c.8817G>T​(p.Gln2939His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TNRC18 NM_001080495.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28487062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC18	NM_001080495.3	c.8817G>T	p.Gln2939His	missense_variant	Exon 30 of 30	ENST00000430969.6	NP_001073964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC18	ENST00000430969.6	c.8817G>T	p.Gln2939His	missense_variant	Exon 30 of 30	5	NM_001080495.3	ENSP00000395538.1
TNRC18	ENST00000399537.8	c.8817G>T	p.Gln2939His	missense_variant	Exon 30 of 30	5		ENSP00000382452.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000124 AC: 3 AN: 241238 Hom.: 0 AF XY: 0.0000229 AC XY: 3 AN XY: 131178

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 SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455990 Hom.: 0 Cov.: 34 AF XY: 0.00000553 AC XY: 4 AN XY: 723850

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000587

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	.;D
Vest4		0.36
MutPred		0.25		Loss of solvent accessibility (P = 0.0128);Loss of solvent accessibility (P = 0.0128);
MVP		0.26
MPC		0.50
ClinPred		0.54	D
GERP RS		3.6
Varity_R		0.36
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs370539555; hg19: chr7-5347827;