Variant 14-68790339-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004926.4(ZFP36L1):c.211C>T(p.Leu71Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000235 in 1,611,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

ZFP36L1
NM_004926.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

ZFP36L1 (HGNC:1107): (ZFP36 ring finger protein like 1) This gene is a member of the TIS11 family of early response genes, which are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. This gene is well conserved across species and has a promoter that contains motifs seen in other early-response genes. The encoded protein contains a distinguishing putative zinc finger domain with a repeating cys-his motif. This putative nuclear transcription factor most likely functions in regulating the response to growth factors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ZFP36L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15534252).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP36L1	NM_004926.4 link	c.211C>T	p.Leu71Phe	missense_variant	Exon 2 of 2	ENST00000439696.3	NP_004917.2	Q07352A0A024R658B3KNA8
ZFP36L1	NM_001244701.1 link	c.418C>T	p.Leu140Phe	missense_variant	Exon 3 of 3		NP_001231630.1	Q07352
ZFP36L1	NM_001244698.2 link	c.211C>T	p.Leu71Phe	missense_variant	Exon 2 of 3		NP_001231627.1	Q07352A0A024R658B3KNA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP36L1	ENST00000439696.3 link	c.211C>T	p.Leu71Phe	missense_variant	Exon 2 of 2	1	NM_004926.4	ENSP00000388402.2		Q07352

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000606

AC:

AN:

247714

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000243

AC:

354

AN:

1459696

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726088

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.000158

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000308

Hom.:

Bravo

AF:

0.000117

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211C>T (p.L71F) alteration is located in exon 2 (coding exon 2) of the ZFP36L1 gene. This alteration results from a C to T substitution at nucleotide position 211, causing the leucine (L) at amino acid position 71 to be replaced by a phenylalanine (F). 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

0.083

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;T;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.032

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

.;T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.38

T;T;T;T;T

Sift4G

Benign

0.72

T;T;.;.;.

Polyphen

0.029

B;B;.;.;.

Vest4

0.27

MVP

0.28

MPC

2.1

ClinPred

0.11

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over