rs781852

chr17-4049808-A-Cchr17-4049808-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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. L1972P) has been classified as Likely benign.

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

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

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=0.082479596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZZEF1	NM_015113.4	c.5915T>G	p.Leu1972Arg	missense_variant	37/55	ENST00000381638.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZZEF1	ENST00000381638.7	c.5915T>G	p.Leu1972Arg	missense_variant	37/55	1	NM_015113.4	P1
ZZEF1	ENST00000571436.5	c.*583T>G		3_prime_UTR_variant, NMD_transcript_variant	8/15	1
ZZEF1	ENST00000573183.1	c.1079T>G	p.Leu360Arg	missense_variant	8/15	2
ZZEF1	ENST00000572426.5	n.2073T>G		non_coding_transcript_exon_variant	12/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	P
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

Publications

LitVar

Other links and lift over

dbSNP: rs781852; hg19: chr17-3953102;