rs12325933

Variant names:

• chr17-78076363-T-C
• rs12325933
• NM_001142640.2:c.3682-822T>C

Variant summary

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

The NM_001142640.2(TNRC6C):​c.3682-822T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,102 control chromosomes in the GnomAD database, including 5,451 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 0.24 (5451 hom., cov: 32)
• Consequence: TNRC6C NM_001142640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6C	NM_001142640.2	c.3682-822T>C		intron_variant	Intron 10 of 22	ENST00000696270.1	NP_001136112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6C	ENST00000696270.1	c.3682-822T>C		intron_variant	Intron 10 of 22		NM_001142640.2	ENSP00000512514.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36802 AN: 151984 Hom.: 5426 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.243 AC: 36885 AN: 152102 Hom.: 5451 Cov.: 32 AF XY: 0.245 AC XY: 18251 AN XY: 74362

African (AFR) AF: 0.397 AC: 16448 AN: 41466

American (AMR) AF: 0.253 AC: 3856 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1926 AN: 5170

South Asian (SAS) AF: 0.313 AC: 1508 AN: 4822

European-Finnish (FIN) AF: 0.169 AC: 1786 AN: 10594

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10054 AN: 67996

Other (OTH) AF: 0.233 AC: 492 AN: 2108

Alfa AF: 0.182 Hom.: 6049

Bravo AF: 0.257

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs12325933; hg19: chr17-76072444;