rs16970829

Variant names:

• chr17-78102100-A-G
• rs16970829
• NM_001142640.2:c.5240-374A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142640.2(TNRC6C):​c.5240-374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,212 control chromosomes in the GnomAD database, including 1,236 homozygotes. 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 0.12 (1236 hom., cov: 32)
• Consequence: TNRC6C NM_001142640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 4 publications found

Genes affected

TNRC6C (HGNC:29318): (trinucleotide repeat containing adaptor 6C) Predicted to enable RNA binding activity. Involved in gene silencing by miRNA; positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; and positive regulation of nuclear-transcribed mRNA poly(A) tail shortening. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142640.2. 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
	TNRC6C	NM_001142640.2	MANE Select	c.5240-374A>G		intron	N/A	NP_001136112.2
	TNRC6C	NM_001395509.1		c.5147-374A>G		intron	N/A	NP_001382438.1
	TNRC6C	NM_001395510.1		c.5123-374A>G		intron	N/A	NP_001382439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6C	ENST00000696270.1	MANE Select	c.5240-374A>G		intron	N/A	ENSP00000512514.1
	TNRC6C	ENST00000935186.1		c.5300-374A>G		intron	N/A	ENSP00000605245.1
	TNRC6C	ENST00000636222.1	TSL:5	c.5264-374A>G		intron	N/A	ENSP00000489933.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17465 AN: 152094 Hom.: 1225 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17513 AN: 152212 Hom.: 1236 Cov.: 32 AF XY: 0.119 AC XY: 8841 AN XY: 74424

African (AFR) AF: 0.185 AC: 7663 AN: 41518

American (AMR) AF: 0.142 AC: 2178 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.136 AC: 703 AN: 5170

South Asian (SAS) AF: 0.128 AC: 618 AN: 4814

European-Finnish (FIN) AF: 0.130 AC: 1382 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4239 AN: 68016

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.0831 Hom.: 854

Bravo AF: 0.122

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16970829; hg19: chr17-76098181;