19-37738674-C-A

Position:

• chr19-37738674-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001172690.2(ZNF573):​c.1816G>T​(p.Gly606Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.00

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF573	NM_001172690.2	c.1816G>T	p.Gly606Cys	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.1816G>T	p.Gly606Cys	missense_variant	5/5	3	NM_001172690.2	ENSP00000440464	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248682 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134562

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Nov 17, 2023

The c.1816G>T (p.G606C) 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 1816, causing the glycine (G) at amino acid position 606 to be replaced by a cysteine (C). 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	0.31
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;T;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.087
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.039	.;T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationTaster	Benign	0.91	D;D;D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-7.3	.;D;D;.;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	.;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	.;D;D;.;D
Vest4		0.40
MVP		0.44
MPC		0.46
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.12
gMVP		0.028

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: rs761495133; hg19: chr19-38229575;