chr19-51873023-C-T

Position:

• chr19-51873023-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370449.1(ZNF577):​c.967G>A​(p.Glu323Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF577 NM_001370449.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

Genes affected

ZNF577 (HGNC:28673): (zinc finger protein 577) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29799268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF577	NM_001370449.1	c.967G>A	p.Glu323Lys	missense_variant	6/6	ENST00000638348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF577	ENST00000638348.2	c.967G>A	p.Glu323Lys	missense_variant	6/6	2	NM_001370449.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 07, 2022

The c.967G>A (p.E323K) alteration is located in exon 7 (coding exon 4) of the ZNF577 gene. This alteration results from a G to A substitution at nucleotide position 967, causing the glutamic acid (E) at amino acid position 323 to be replaced by a lysine (K). 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.096	T;.;.;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.11	T;.;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L;.;.;.
MutationTaster	Benign	0.61	D;D;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D;.;D;.
REVEL	Benign	0.12
Sift	Benign	0.16	T;.;D;.
Sift4G	Benign	0.13	T;.;T;.
Polyphen		1.0	D;P;P;.
Vest4		0.27
MutPred		0.36		Gain of methylation at E323 (P = 0.0036);.;.;Gain of methylation at E323 (P = 0.0036);
MVP		0.34
MPC		0.45
ClinPred		0.97	D
GERP RS		3.1
Varity_R		0.46
gMVP		0.017

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: chr19-52376276;