NM_015113.4:c.5915T>G

Variant names:

• chr17-4049808-A-C
• rs781852
• NM_015113.4:c.5915T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015113.4(ZZEF1):​c.5915T>G​(p.Leu1972Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZZEF1 NM_015113.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 47 publications found

Genes affected

ZZEF1 (HGNC:29027): (zinc finger ZZ-type and EF-hand domain containing 1) Predicted to enable ubiquitin-like protein ligase activity. Predicted to act upstream of or within several processes, including glutamatergic synaptic transmission; regulation of peptidyl-tyrosine phosphorylation; and visual learning. Predicted to be located in cell surface; postsynapse; and presynaptic active zone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082479596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015113.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZZEF1	NM_015113.4	MANE Select	c.5915T>G	p.Leu1972Arg	missense	Exon 37 of 55	NP_055928.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZZEF1	ENST00000381638.7	TSL:1 MANE Select	c.5915T>G	p.Leu1972Arg	missense	Exon 37 of 55	ENSP00000371051.2
	ZZEF1	ENST00000571436.5	TSL:1	n.*583T>G		non_coding_transcript_exon	Exon 8 of 15	ENSP00000459023.1
	ZZEF1	ENST00000571436.5	TSL:1	n.*583T>G		3_prime_UTR	Exon 8 of 15	ENSP00000459023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.16
Sift	Benign	0.059	T
Sift4G	Benign	0.16	T
Polyphen		0.055	B
Vest4		0.12
MutPred		0.098		Gain of solvent accessibility (P = 0.0086)
MVP		0.043
MPC		0.23
ClinPred		0.40	T
GERP RS		5.5
Varity_R		0.052
gMVP		0.22

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: rs781852; hg19: chr17-3953102;