19-9653169-G-C

Variant names:

• chr19-9653169-G-C
• NM_001130031.2:c.1061C>G

Variant summary

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

The NM_001130031.2(ZNF562):​c.1061C>G​(p.Thr354Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF562 NM_001130031.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.95

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=0.036655515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF562	NM_001130031.2	c.1061C>G	p.Thr354Ser	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.1061C>G	p.Thr354Ser	missense_variant	Exon 6 of 6	3	NM_001130031.2	ENSP00000410734.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1061C>G (p.T354S) alteration is located in exon 6 (coding exon 5) of the ZNF562 gene. This alteration results from a C to G substitution at nucleotide position 1061, causing the threonine (T) at amino acid position 354 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.75
DANN	Benign	0.79
DEOGEN2	Benign	0.00058	.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.18	T;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.037	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.28	.;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.080	N;N;.
REVEL	Benign	0.017
Sift	Benign	0.82	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.073	B;B;.
Vest4		0.049
MutPred		0.42		.;Gain of catalytic residue at T354 (P = 0.0821);.;
MVP		0.076
ClinPred		0.053	T
GERP RS		-2.9
Varity_R		0.030
gMVP		0.027

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: chr19-9763845;