chr19-9653739-C-T

Variant names:

• chr19-9653739-C-T
• rs760986308
• NM_001130031.2:c.491G>A

Variant summary

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

The NM_001130031.2(ZNF562):​c.491G>A​(p.Ser164Asn) 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: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF562 NM_001130031.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04

Genes affected

ZNF562 (HGNC:25950): (zinc finger protein 562) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF561-AS1 (HGNC:27613): (ZNF561 antisense RNA 1 (head to head))

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=0.057724386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF562	NM_001130031.2	c.491G>A	p.Ser164Asn	missense_variant	Exon 6 of 6	ENST00000453372.7	NP_001123503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF562	ENST00000453372.7	c.491G>A	p.Ser164Asn	missense_variant	Exon 6 of 6	3	NM_001130031.2	ENSP00000410734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251278 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135802

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000410 AC: 6 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727192

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.491G>A (p.S164N) alteration is located in exon 6 (coding exon 5) of the ZNF562 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the serine (S) at amino acid position 164 to be replaced by an asparagine (N). 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	0.15
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.075
DANN	Benign	0.70
DEOGEN2	Benign	0.0081	.;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.00040	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.39	.;N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.93	N;N;.
REVEL	Benign	0.016
Sift	Benign	0.17	T;T;.
Sift4G	Benign	0.17	T;T;T
Polyphen		0.40	B;B;.
Vest4		0.038
MutPred		0.23		.;Loss of disorder (P = 0.0883);.;
MVP		0.085
ClinPred		0.045	T
GERP RS		-2.9
Varity_R		0.037
gMVP		0.024

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: rs760986308; hg19: chr19-9764415;