chr17-78076363-T-C

Position:

• chr17-78076363-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6C	NM_001142640.2	c.3682-822T>C		intron_variant		ENST00000696270.1	NP_001136112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6C	ENST00000696270.1	c.3682-822T>C		intron_variant			NM_001142640.2	ENSP00000512514	P4

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

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.233

Alfa AF: 0.165 Hom.: 3736

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

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: rs12325933; hg19: chr17-76072444;