chr19-2917130-G-A

Position:

• chr19-2917130-G-A

Variant summary

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

The NM_173480.3(ZNF57):​c.509G>A​(p.Gly170Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF57 NM_173480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99

Genes affected

ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ENSG00000253392 (HGNC:):

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
ZNF57	NM_173480.3	c.509G>A	p.Gly170Asp	missense_variant	4/4	ENST00000306908.10	NP_775751.1
ZNF57	NM_001319083.2	c.413G>A	p.Gly138Asp	missense_variant	4/4		NP_001306012.1
ZNF57	XM_011527682.3	c.413G>A	p.Gly138Asp	missense_variant	4/4		XP_011525984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF57	ENST00000306908.10	c.509G>A	p.Gly170Asp	missense_variant	4/4	1	NM_173480.3	ENSP00000303696.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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

Jun 29, 2023

The c.509G>A (p.G170D) alteration is located in exon 4 (coding exon 4) of the ZNF57 gene. This alteration results from a G to A substitution at nucleotide position 509, causing the glycine (G) at amino acid position 170 to be replaced by an aspartic acid (D). 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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.0028	.;T;T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.35	T;T;T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.32	.;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.047	.;D;D;T;.
Sift4G	Uncertain	0.0030	D;D;T;D;T
Polyphen		0.0	.;B;.;.;.
Vest4		0.25
MutPred		0.41		.;Loss of glycosylation at K174 (P = 0.1594);.;.;.;
MVP		0.24
MPC		0.041
ClinPred		0.13	T
GERP RS		0.92
Varity_R		0.028
gMVP		0.015

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -38

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2088209045; hg19: chr19-2917128;