rs12601622

Positions:

• chr17-78053294-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142640.2(TNRC6C):​c.3016+1846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,216 control chromosomes in the GnomAD database, including 46 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 0.019 (46 hom., cov: 32)
• Consequence: TNRC6C NM_001142640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6C	NM_001142640.2	c.3016+1846G>A		intron_variant		ENST00000696270.1	NP_001136112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6C	ENST00000696270.1	c.3016+1846G>A		intron_variant			NM_001142640.2	ENSP00000512514	P4

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2888 AN: 152098 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0786

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0190 AC: 2889 AN: 152216 Hom.: 46 Cov.: 32 AF XY: 0.0189 AC XY: 1405 AN XY: 74438

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0197 Hom.: 9

Bravo AF: 0.0190

Asia WGS AF: 0.0520 AC: 182 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	1.1
DANN	Benign	0.57

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: rs12601622; hg19: chr17-76049375;