17-78096472-G-C

Variant names:

• chr17-78096472-G-C
• rs2311001
• NM_001142640.2:c.4928-1273G>C

Variant summary

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

The NM_001142640.2(TNRC6C):​c.4928-1273G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,084 control chromosomes in the GnomAD database, including 17,809 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 0.46 (17809 hom., cov: 33)
• Consequence: TNRC6C NM_001142640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6C	NM_001142640.2	c.4928-1273G>C		intron_variant	Intron 18 of 22	ENST00000696270.1	NP_001136112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6C	ENST00000696270.1	c.4928-1273G>C		intron_variant	Intron 18 of 22		NM_001142640.2	ENSP00000512514.1
TNRC6C	ENST00000636222.1	c.4952-1273G>C		intron_variant	Intron 18 of 22	5		ENSP00000489933.1
TNRC6C	ENST00000696541.1	c.4928-1871G>C		intron_variant	Intron 18 of 21			ENSP00000512702.1
TNRC6C	ENST00000588061.6	c.4457-1871G>C		intron_variant	Intron 14 of 17	5		ENSP00000468647.2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70409 AN: 151966 Hom.: 17763 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.464 AC: 70522 AN: 152084 Hom.: 17809 Cov.: 33 AF XY: 0.467 AC XY: 34689 AN XY: 74324

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.473

Alfa AF: 0.414 Hom.: 1753

Bravo AF: 0.483

Asia WGS AF: 0.512 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.42

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: rs2311001; hg19: chr17-76092553;