NM_001142640.2:c.4927+1336A>C

Variant names:

• chr17-78095099-A-C
• rs16970811
• NM_001142640.2:c.4927+1336A>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.4927+1336A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,292 control chromosomes in the GnomAD database, including 1,049 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 0.11 (1049 hom., cov: 32)
• Consequence: TNRC6C NM_001142640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6C	NM_001142640.2	MANE Select	c.4927+1336A>C		intron	N/A	NP_001136112.2
	TNRC6C	NM_001395509.1		c.4951+1336A>C		intron	N/A	NP_001382438.1
	TNRC6C	NM_001395510.1		c.4927+1336A>C		intron	N/A	NP_001382439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6C	ENST00000696270.1	MANE Select	c.4927+1336A>C		intron	N/A	ENSP00000512514.1
	TNRC6C	ENST00000636222.1	TSL:5	c.4951+1336A>C		intron	N/A	ENSP00000489933.1
	TNRC6C	ENST00000696541.1		c.4927+1336A>C		intron	N/A	ENSP00000512702.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16074 AN: 152174 Hom.: 1044 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.106 AC: 16089 AN: 152292 Hom.: 1049 Cov.: 32 AF XY: 0.105 AC XY: 7793 AN XY: 74476

African (AFR) AF: 0.173 AC: 7189 AN: 41550

American (AMR) AF: 0.0933 AC: 1428 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.181 AC: 934 AN: 5174

South Asian (SAS) AF: 0.142 AC: 686 AN: 4824

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5105 AN: 68032

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.102 Hom.: 198

Bravo AF: 0.114

Asia WGS AF: 0.179 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.32
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: rs16970811; hg19: chr17-76091180; COSMIC: COSV107379806; COSMIC: COSV107379806;