14-68789856-G-C

Variant names:

• chr14-68789856-G-C
• NM_004926.4:c.694C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004926.4(ZFP36L1):​c.694C>G​(p.Leu232Val) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP36L1 NM_004926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13847625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP36L1	NM_004926.4	c.694C>G	p.Leu232Val	missense_variant	Exon 2 of 2	ENST00000439696.3	NP_004917.2
ZFP36L1	NM_001244701.1	c.901C>G	p.Leu301Val	missense_variant	Exon 3 of 3		NP_001231630.1
ZFP36L1	NM_001244698.2	c.694C>G	p.Leu232Val	missense_variant	Exon 2 of 3		NP_001231627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP36L1	ENST00000439696.3	c.694C>G	p.Leu232Val	missense_variant	Exon 2 of 2	1	NM_004926.4	ENSP00000388402.2
ZFP36L1	ENST00000336440.4	c.694C>G	p.Leu232Val	missense_variant	Exon 2 of 3	2		ENSP00000337386.3
ZFP36L1	ENST00000555997.1	n.898C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694C>G (p.L232V) alteration is located in exon 2 (coding exon 2) of the ZFP36L1 gene. This alteration results from a C to G substitution at nucleotide position 694, causing the leucine (L) at amino acid position 232 to be replaced by a valine (V). 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	0.091
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.082	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.39	N;N
REVEL	Benign	0.072
Sift	Benign	0.080	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.85	P;P
Vest4		0.038
MutPred		0.42		Gain of catalytic residue at P228 (P = 0);Gain of catalytic residue at P228 (P = 0);
MVP		0.18
MPC		1.2
ClinPred		0.22	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-69256573;