NM_004926.4:c.826A>C

Variant names:

• chr14-68789724-T-G
• rs765865743
• NM_004926.4:c.826A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004926.4(ZFP36L1):​c.826A>C​(p.Thr276Pro) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T276A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP36L1 NM_004926.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054738373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP36L1	NM_004926.4	MANE Select	c.826A>C	p.Thr276Pro	missense	Exon 2 of 2	NP_004917.2
	ZFP36L1	NM_001244701.1		c.1033A>C	p.Thr345Pro	missense	Exon 3 of 3	NP_001231630.1	Q07352
	ZFP36L1	NM_001244698.2		c.826A>C	p.Thr276Pro	missense	Exon 2 of 3	NP_001231627.1	Q07352

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP36L1	ENST00000439696.3	TSL:1 MANE Select	c.826A>C	p.Thr276Pro	missense	Exon 2 of 2	ENSP00000388402.2	Q07352
	ZFP36L1	ENST00000336440.5	TSL:2	c.826A>C	p.Thr276Pro	missense	Exon 2 of 3	ENSP00000337386.3
	ZFP36L1	ENST00000555997.1	TSL:3	n.1030A>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.17
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.0050
Sift	Benign	0.25	T
Sift4G	Benign	0.36	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.30		Gain of catalytic residue at S273 (P = 2e-04)
MVP		0.068
MPC		1.4
ClinPred		0.066	T
GERP RS		0.60
Varity_R		0.17
gMVP		0.21
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs765865743; hg19: chr14-69256441;