7-5316217-C-G

Variant names:

• chr7-5316217-C-G
• rs4236384
• NM_001080495.3:c.6746-145G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080495.3(TNRC18):​c.6746-145G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNRC18 NM_001080495.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC18	NM_001080495.3	c.6746-145G>C		intron_variant	Intron 24 of 29	ENST00000430969.6	NP_001073964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC18	ENST00000430969.6	c.6746-145G>C		intron_variant	Intron 24 of 29	5	NM_001080495.3	ENSP00000395538.1
TNRC18	ENST00000399537.8	c.6746-145G>C		intron_variant	Intron 24 of 29	5		ENSP00000382452.4
TNRC18	ENST00000328270.3	c.185-145G>C		intron_variant	Intron 2 of 4	5		ENSP00000329902.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149862 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000129 AC: 5 AN: 387712 Hom.: 0 AF XY: 0.0000146 AC XY: 3 AN XY: 205960

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8058

American (AMR) AF: 0.00 AC: 0 AN: 8914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12818

East Asian (EAS) AF: 0.00 AC: 0 AN: 23034

South Asian (SAS) AF: 0.00 AC: 0 AN: 34112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1844

European-Non Finnish (NFE) AF: 0.0000122 AC: 3 AN: 245926

Other (OTH) AF: 0.0000874 AC: 2 AN: 22874

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149862 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 72916

African (AFR) AF: 0.00 AC: 0 AN: 40450

American (AMR) AF: 0.00 AC: 0 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67848

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 11201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.55
PhyloP100		-0.83
Mutation Taster		=100/0	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: rs4236384; hg19: chr7-5355848;