chr17-5182324-T-A

Variant names:

• chr17-5182324-T-A
• rs369230201
• NM_032530.2:c.1933A>T

Variant summary

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

The NM_032530.2(ZNF594):​c.1933A>T​(p.Ile645Phe) 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 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. I645V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF594 NM_032530.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

Genes affected

ZNF594 (HGNC:29392): (zinc finger protein 594) Predicted to enable DNA-binding transcription activator 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. Located in nucleoplasm. [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=0.25103742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF594	NM_032530.2	c.1933A>T	p.Ile645Phe	missense_variant	Exon 2 of 2	ENST00000575779.2	NP_115919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF594	ENST00000575779.2	c.1933A>T	p.Ile645Phe	missense_variant	Exon 2 of 2	3	NM_032530.2	ENSP00000461032.1
ZNF594	ENST00000399604.4	c.1933A>T	p.Ile645Phe	missense_variant	Exon 1 of 1	6		ENSP00000382513.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

African (AFR) AF: 0.0000299 AC: 1 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.2
DANN	Benign	0.93
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.000010	N
LIST_S2	Benign	0.16	.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		-1.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.3	D;.
REVEL	Benign	0.046
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		0.92	P;P
Vest4		0.11
MutPred		0.52		Loss of stability (P = 0.0356);Loss of stability (P = 0.0356);
MVP		0.14
MPC		0.020
ClinPred		0.37	T
GERP RS		-1.4
Varity_R		0.26
gMVP		0.0064

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: rs369230201; hg19: chr17-5085619;