19-39407827-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003407.5(ZFP36):c.109C>T(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,605,664 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0090 (26 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (14 hom.)
• Consequence: ZFP36 NM_003407.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023907125).
• BP6: Variant 19-39407827-C-T is Benign according to our data. Variant chr19-39407827-C-T is described in ClinVar as [Benign]. Clinvar id is 785623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00901 (1372/152290) while in subpopulation AFR AF= 0.031 (1286/41548). AF 95% confidence interval is 0.0295. There are 26 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP36	NM_003407.5	c.109C>T	p.Pro37Ser	missense_variant	2/2	ENST00000597629.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP36	ENST00000597629.3	c.109C>T	p.Pro37Ser	missense_variant	2/2	1	NM_003407.5	P4

Frequencies

GnomAD3 genomes AF: 0.00900 AC: 1369 AN: 152172 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00234 AC: 561 AN: 239538 Hom.: 6 AF XY: 0.00158 AC XY: 206 AN XY: 130776

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000157

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.000964 AC: 1401 AN: 1453374 Hom.: 14 Cov.: 31 AF XY: 0.000871 AC XY: 630 AN XY: 723090

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000829

Gnomad4 OTH exome AF: 0.00214

GnomAD4 genome AF: 0.00901 AC: 1372 AN: 152290 Hom.: 26 Cov.: 32 AF XY: 0.00862 AC XY: 642 AN XY: 74456

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00198 Hom.: 3

Bravo AF: 0.00996

ESP6500AA AF: 0.0297 AC: 131

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00291 AC: 353

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	14
Dann	Uncertain	0.98
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.44	T
Vest4		0.039
MVP		0.043
MPC		0.42
ClinPred		0.0026	T
GERP RS		1.4

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: rs17878633; hg19: chr19-39898467;