5-178931376-A-C

Variant names:

• chr5-178931376-A-C
• rs1758833143
• NM_030613.4:c.63A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030613.4(ZFP2):​c.63A>C​(p.Leu21Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFP2 NM_030613.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.583

Genes affected

ZFP2 (HGNC:26138): (ZFP2 zinc finger protein) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057504326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP2	NM_030613.4	c.63A>C	p.Leu21Phe	missense_variant	Exon 5 of 5	ENST00000361362.7	NP_085116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP2	ENST00000361362.7	c.63A>C	p.Leu21Phe	missense_variant	Exon 5 of 5	1	NM_030613.4	ENSP00000354453.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461684 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.63A>C (p.L21F) alteration is located in exon 5 (coding exon 1) of the ZFP2 gene. This alteration results from a A to C substitution at nucleotide position 63, causing the leucine (L) at amino acid position 21 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	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.037	T;.;T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.44	.;T;.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.82	L;.;L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N;D;N;N
REVEL	Benign	0.015
Sift	Benign	0.50	T;.;T;T
Sift4G	Benign	0.26	T;D;T;T
Polyphen		0.0030	B;.;B;B
Vest4		0.10
MutPred		0.24		Loss of disorder (P = 0.1557);Loss of disorder (P = 0.1557);Loss of disorder (P = 0.1557);Loss of disorder (P = 0.1557);
MVP		0.076
MPC		0.034
ClinPred		0.063	T
GERP RS		1.9
Varity_R		0.067
gMVP		0.091

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: rs1758833143; hg19: chr5-178358377;