19-2917127-C-A

Variant names:

• chr19-2917127-C-A
• NM_173480.3:c.506C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173480.3(ZNF57):​c.506C>A​(p.Pro169Gln) 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. 15/21 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: -4.63

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024215937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF57	NM_173480.3	c.506C>A	p.Pro169Gln	missense_variant	Exon 4 of 4	ENST00000306908.10	NP_775751.1
ZNF57	NM_001319083.2	c.410C>A	p.Pro137Gln	missense_variant	Exon 4 of 4		NP_001306012.1
ZNF57	XM_011527682.3	c.410C>A	p.Pro137Gln	missense_variant	Exon 4 of 4		XP_011525984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF57	ENST00000306908.10	c.506C>A	p.Pro169Gln	missense_variant	Exon 4 of 4	1	NM_173480.3	ENSP00000303696.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.506C>A (p.P169Q) alteration is located in exon 4 (coding exon 4) of the ZNF57 gene. This alteration results from a C to A substitution at nucleotide position 506, causing the proline (P) at amino acid position 169 to be replaced by a glutamine (Q). 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	0.075
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.71
DEOGEN2	Benign	0.00016	.;T;T;T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.088	T;T;T;T;T
M_CAP	Benign	0.00041	T
MetaRNN	Benign	0.024	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;.;.
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.87	.;N;N;N;.
REVEL	Benign	0.022
Sift	Benign	0.89	.;T;T;T;.
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.
Vest4		0.13
MutPred		0.21		.;Loss of catalytic residue at P168 (P = 0.0121);.;.;.;
MVP		0.088
MPC		0.028
ClinPred		0.038	T
GERP RS		-4.0
Varity_R		0.013
gMVP		0.0094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-2917125;