5-178931702-A-T

Variant names:

• chr5-178931702-A-T
• rs756330356
• NM_030613.4:c.389A>T

Variant summary

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

The NM_030613.4(ZFP2):​c.389A>T​(p.Tyr130Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y130C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP2 NM_030613.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856
• Publications: 0 publications found

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]

ZNF454-DT (HGNC:55213): (ZNF454 divergent transcript)

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=0.039850563).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030613.4. 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
	ZFP2	NM_030613.4	MANE Select	c.389A>T	p.Tyr130Phe	missense	Exon 5 of 5	NP_085116.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP2	ENST00000361362.7	TSL:1 MANE Select	c.389A>T	p.Tyr130Phe	missense	Exon 5 of 5	ENSP00000354453.2	Q6ZN57
	ZFP2	ENST00000523286.1	TSL:1	c.389A>T	p.Tyr130Phe	missense	Exon 5 of 5	ENSP00000430531.1	Q6ZN57
	ZFP2	ENST00000520301.5	TSL:5	c.389A>T	p.Tyr130Phe	missense	Exon 4 of 4	ENSP00000430980.1	Q6ZN57

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461826 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.7
DANN	Benign	0.59
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00096	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.86
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.056
Sift	Benign	0.22	T
Sift4G	Benign	0.17	T
Polyphen		0.0030	B
Vest4		0.15
MutPred		0.56		Loss of phosphorylation at Y130 (P = 0.0916)
MVP		0.055
MPC		0.031
ClinPred		0.094	T
GERP RS		-5.9
Varity_R		0.13
gMVP		0.042
Mutation Taster		=100/0	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: rs756330356; hg19: chr5-178358703;