19-37738646-C-A

Position:

• chr19-37738646-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001172690.2(ZNF573):​c.1844G>T​(p.Cys615Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF573 NM_001172690.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81

Genes affected

ZNF573 (HGNC:26420): (zinc finger protein 573) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF573	NM_001172690.2	c.1844G>T	p.Cys615Phe	missense_variant	5/5	ENST00000536220.7	NP_001166161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF573	ENST00000536220.7	c.1844G>T	p.Cys615Phe	missense_variant	5/5	3	NM_001172690.2	ENSP00000440464	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

The c.1844G>T (p.C615F) alteration is located in exon 5 (coding exon 4) of the ZNF573 gene. This alteration results from a G to T substitution at nucleotide position 1844, causing the cysteine (C) at amino acid position 615 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	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;.;.;T;.
Eigen	Benign	0.055
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.34	.;T;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Pathogenic	0.86	D;D;D;D;D
MetaSVM	Uncertain	0.31	D
MutationTaster	Benign	0.52	D;D;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-10	.;D;D;.;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	.;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.59, 0.33	.;P;B;.;B
Vest4		0.50
MVP		0.88
MPC		0.55
ClinPred		0.96	D
GERP RS		1.3
Varity_R		0.11
gMVP		0.065

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-38229547;