19-57858632-C-A

Variant names:

• chr19-57858632-C-A
• ENST00000593873.6:c.90C>A

Variant summary

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

The ENST00000593873.6(ENSG00000268750):​c.90C>A​(p.Tyr30*) variant causes a stop gained 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000268750 ENST00000593873.6 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.67

Genes affected

ENSG00000268750 (HGNC:):

ZNF587 (HGNC:30955): (zinc finger protein 587) 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]

ZNF814 (HGNC:33258): (zinc finger protein 814) Predicted to enable DNA-binding transcription activator 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 rank	MANE	Protein	UniProt
ZNF587	NM_032828.4	c.220C>A	p.Gln74Lys	missense_variant	Exon 3 of 3	ENST00000339656.8	NP_116217.1
ZNF587	NM_001204817.2	c.217C>A	p.Gln73Lys	missense_variant	Exon 3 of 3		NP_001191746.1
LOC124904782	XR_007067358.1	n.-56G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000268750	ENST00000593873.6	c.90C>A	p.Tyr30*	stop_gained	Exon 2 of 2	4		ENSP00000469133.2
ZNF587	ENST00000339656.8	c.220C>A	p.Gln74Lys	missense_variant	Exon 3 of 3	1	NM_032828.4	ENSP00000345479.4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1390630 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685580

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.220C>A (p.Q74K) alteration is located in exon 3 (coding exon 3) of the ZNF587 gene. This alteration results from a C to A substitution at nucleotide position 220, causing the glutamine (Q) at amino acid position 74 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.28
DANN	Benign	0.86
DEOGEN2	Benign	0.0047	.;.;.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.28	T;T;T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.080	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.84	.;.;.;L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	.;.;.;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.20	.;.;.;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0020	.;.;.;B;.;.
Vest4		0.073, 0.078, 0.088
MutPred		0.28		.;.;Gain of methylation at Q74 (P = 0.0019);Gain of methylation at Q74 (P = 0.0019);.;.;
MVP		0.048
MPC		1.4
ClinPred		0.16	T
GERP RS		-2.8
Varity_R		0.094
gMVP		0.015

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: chr19-58370000;