19-39406926-G-C

Position:

• chr19-39406926-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003407.5(ZFP36):​c.22G>C​(p.Glu8Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP36 NM_003407.5 missense, splice_region
• Scores: Splicing: ADA: 0.0002497
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

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]

ZFP36 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050694764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP36	NM_003407.5	c.22G>C	p.Glu8Gln	missense_variant, splice_region_variant	1/2	ENST00000597629.3	NP_003398.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP36	ENST00000597629.3	c.22G>C	p.Glu8Gln	missense_variant, splice_region_variant	1/2	1	NM_003407.5	ENSP00000469647.2
ZFP36	ENST00000594045.2	c.22G>C	p.Glu8Gln	missense_variant	1/2	3		ENSP00000472329.2
ZFP36	ENST00000594442.2	c.40G>C	p.Glu14Gln	missense_variant, splice_region_variant	1/2	5
ZFP36	ENST00000652583.1	n.69G>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 25, 2024

The c.22G>C (p.E8Q) alteration is located in exon 1 (coding exon 1) of the ZFP36 gene. This alteration results from a G to C substitution at nucleotide position 22, causing the glutamic acid (E) at amino acid position 8 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Benign	0.96
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.57	T;.
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.43	T;.
Vest4		0.41
MVP		0.043
MPC		0.43
ClinPred		0.092	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.0020
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-39897566;