chr19-37413408-T-C

Position:

• chr19-37413408-T-C

Variant summary

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

The NM_152484.3(ZNF569):​c.1250A>G​(p.Lys417Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF569 NM_152484.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

Genes affected

ZNF569 (HGNC:24737): (zinc finger protein 569) 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 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
ZNF569	NM_152484.3	c.1250A>G	p.Lys417Arg	missense_variant	6/6	ENST00000316950.11	NP_689697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF569	ENST00000316950.11	c.1250A>G	p.Lys417Arg	missense_variant	6/6	1	NM_152484.3	ENSP00000325018	P2
ZNF569	ENST00000392149.6	c.1250A>G	p.Lys417Arg	missense_variant	5/5	1		ENSP00000375992	P2
ZNF569	ENST00000392150.2	c.773A>G	p.Lys258Arg	missense_variant	2/2	1		ENSP00000375993
ZNF569	ENST00000448051.7	c.1322A>G	p.Lys441Arg	missense_variant	9/9	2		ENSP00000466221	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

May 17, 2023

The c.1250A>G (p.K417R) alteration is located in exon 6 (coding exon 4) of the ZNF569 gene. This alteration results from a A to G substitution at nucleotide position 1250, causing the lysine (K) at amino acid position 417 to be replaced by an arginine (R). 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	0.16
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.021	.;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.76	P;P;.
Vest4		0.43
MutPred		0.51		Loss of methylation at K417 (P = 0.0027);Loss of methylation at K417 (P = 0.0027);.;
MVP		0.56
MPC		0.52
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.25
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-37904310;