chr17-78097785-T-C

Variant names:

• chr17-78097785-T-C
• rs2290906
• NM_001142640.2:c.4968T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001142640.2(TNRC6C):​c.4968T>C​(p.Ser1656Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,550,700 control chromosomes in the GnomAD database, including 27,346 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 0.23 (4712 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22634 hom.)
• Consequence: TNRC6C NM_001142640.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 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.4968T>C	p.Ser1656Ser	synonymous	Exon 19 of 23	NP_001136112.2
	TNRC6C	NM_001395511.1		c.4362T>C	p.Ser1454Ser	synonymous	Exon 16 of 20	NP_001382440.1
	TNRC6C	NM_001395508.1		c.4338T>C	p.Ser1446Ser	synonymous	Exon 16 of 20	NP_001382437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6C	ENST00000696270.1	MANE Select	c.4968T>C	p.Ser1656Ser	synonymous	Exon 19 of 23	ENSP00000512514.1
	TNRC6C	ENST00000636222.1	TSL:5	c.4992T>C	p.Ser1664Ser	synonymous	Exon 19 of 23	ENSP00000489933.1
	TNRC6C	ENST00000696541.1		c.4928-558T>C		intron	N/A	ENSP00000512702.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34765 AN: 152108 Hom.: 4693 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.220 AC: 34418 AN: 156270 AF XY: 0.221

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.348

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.169 AC: 236229 AN: 1398474 Hom.: 22634 Cov.: 32 AF XY: 0.172 AC XY: 118489 AN XY: 689730

African (AFR) AF: 0.362 AC: 11426 AN: 31572

American (AMR) AF: 0.290 AC: 10322 AN: 35650

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4107 AN: 25172

East Asian (EAS) AF: 0.311 AC: 11119 AN: 35714

South Asian (SAS) AF: 0.298 AC: 23561 AN: 79174

European-Finnish (FIN) AF: 0.160 AC: 7807 AN: 48908

Middle Eastern (MID) AF: 0.255 AC: 1453 AN: 5698

European-Non Finnish (NFE) AF: 0.143 AC: 154758 AN: 1078612

Other (OTH) AF: 0.201 AC: 11676 AN: 57974

GnomAD4 genome AF: 0.229 AC: 34833 AN: 152226 Hom.: 4712 Cov.: 33 AF XY: 0.232 AC XY: 17295 AN XY: 74434

African (AFR) AF: 0.355 AC: 14727 AN: 41512

American (AMR) AF: 0.250 AC: 3822 AN: 15300

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

East Asian (EAS) AF: 0.324 AC: 1676 AN: 5178

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1776 AN: 10608

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10052 AN: 68022

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.171 Hom.: 2188

Bravo AF: 0.242

Asia WGS AF: 0.347 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		0.40
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2290906; hg19: chr17-76093866; COSMIC: COSV56940523; COSMIC: COSV56940523;