19-39408027-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_003407.5(ZFP36):c.309C>T(p.Arg103=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,613,562 control chromosomes in the GnomAD database, including 1,318 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 0.038 (116 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1202 hom.)
• Consequence: ZFP36 NM_003407.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

Genes affected

ZFP36 (HGNC:12862): (ZFP36 ring finger protein) Enables several functions, including 14-3-3 protein binding activity; heat shock protein binding activity; and mRNA 3'-UTR AU-rich region binding activity. Involved in several processes, including cellular response to cytokine stimulus; cellular response to growth factor stimulus; and regulation of gene expression. Acts upstream of or within mRNA catabolic process. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleus. Part of ribonucleoprotein complex. Colocalizes with RISC-loading complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0377 (5741/152282) while in subpopulation NFE AF= 0.0405 (2751/68006). AF 95% confidence interval is 0.0392. There are 116 homozygotes in gnomad4. There are 2756 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 111 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP36	NM_003407.5	c.309C>T	p.Arg103=	synonymous_variant	2/2	ENST00000597629.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP36	ENST00000597629.3	c.309C>T	p.Arg103=	synonymous_variant	2/2	1	NM_003407.5	P4

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5720 AN: 152164 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0468

GnomAD3 exomes AF: 0.0351 AC: 8734 AN: 249002 Hom.: 180 AF XY: 0.0356 AC XY: 4807 AN XY: 135052

Gnomad AFR exome AF: 0.0374

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.0546

Gnomad EAS exome AF: 0.0401

Gnomad SAS exome AF: 0.0319

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.0401

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0399 AC: 58264 AN: 1461280 Hom.: 1202 Cov.: 31 AF XY: 0.0394 AC XY: 28661 AN XY: 727000

Gnomad4 AFR exome AF: 0.0406

Gnomad4 AMR exome AF: 0.0251

Gnomad4 ASJ exome AF: 0.0545

Gnomad4 EAS exome AF: 0.0346

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.0179

Gnomad4 NFE exome AF: 0.0419

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0377 AC: 5741 AN: 152282 Hom.: 116 Cov.: 32 AF XY: 0.0370 AC XY: 2756 AN XY: 74458

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0405

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0337 Hom.: 60

Bravo AF: 0.0398

Asia WGS AF: 0.0400 AC: 142 AN: 3478

EpiCase AF: 0.0442

EpiControl AF: 0.0464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	7.2
Dann	Benign	0.87

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: rs3746083; hg19: chr19-39898667; COSMIC: COSV50527647; COSMIC: COSV50527647;