19-57858627-C-T

Variant names:

• chr19-57858627-C-T
• NM_032828.4:c.215C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032828.4(ZNF587):​c.215C>T​(p.Ser72Phe) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: ZNF587 NM_032828.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.148

Genes affected

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]

ENSG00000268750 (HGNC:):

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1627503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF587	NM_032828.4	c.215C>T	p.Ser72Phe	missense_variant	Exon 3 of 3	ENST00000339656.8	NP_116217.1
ZNF587	NM_001204817.2	c.212C>T	p.Ser71Phe	missense_variant	Exon 3 of 3		NP_001191746.1
LOC124904782	XR_007067358.1	n.-51G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF587	ENST00000339656.8	c.215C>T	p.Ser72Phe	missense_variant	Exon 3 of 3	1	NM_032828.4	ENSP00000345479.4
ENSG00000268750	ENST00000593873.6	c.85C>T	p.Leu29Leu	synonymous_variant	Exon 2 of 2	4		ENSP00000469133.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215C>T (p.S72F) alteration is located in exon 3 (coding exon 3) of the ZNF587 gene. This alteration results from a C to T substitution at nucleotide position 215, causing the serine (S) at amino acid position 72 to be replaced by a phenylalanine (F). 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	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.83
DEOGEN2	Benign	0.037	.;.;.;T;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.67	T;T;T;T;T;D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;.;.;L;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.0	.;.;.;D;D;D
REVEL	Benign	0.034
Sift	Uncertain	0.013	.;.;.;D;D;D
Sift4G	Benign	0.26	T;T;T;D;T;D
Polyphen		0.97	.;.;.;D;.;.
Vest4		0.070, 0.11, 0.080
MutPred		0.38		.;.;Loss of disorder (P = 0.0044);Loss of disorder (P = 0.0044);.;.;
MVP		0.36
MPC		0.91
ClinPred		0.33	T
GERP RS		1.4
Varity_R		0.074
gMVP		0.0083

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: chr19-58369995;