19-57859040-A-C

Variant names:

• chr19-57859040-A-C
• rs768568016
• NM_032828.4:c.628A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032828.4(ZNF587):​c.628A>C​(p.Thr210Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T210A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 27)
• Consequence: ZNF587 NM_032828.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 0 publications found

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]

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]

ENSG00000268750 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074596226).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF587	NM_032828.4	MANE Select	c.628A>C	p.Thr210Pro	missense	Exon 3 of 3	NP_116217.1	Q96SQ5-1
	ZNF587	NM_001204817.2		c.625A>C	p.Thr209Pro	missense	Exon 3 of 3	NP_001191746.1	Q96SQ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF587	ENST00000339656.8	TSL:1 MANE Select	c.628A>C	p.Thr210Pro	missense	Exon 3 of 3	ENSP00000345479.4	Q96SQ5-1
	ZNF587	ENST00000423137.1	TSL:1	c.625A>C	p.Thr209Pro	missense	Exon 3 of 3	ENSP00000393865.1	Q96SQ5-2
	ZNF814	ENST00000596604.5	TSL:1	c.164-8479T>G		intron	N/A	ENSP00000470328.1	M0QZ64

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.8
DANN	Benign	0.43
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.0074	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.49
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.0090
Sift	Benign	0.044	D
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.26		Loss of MoRF binding (P = 0.0761)
MVP		0.30
MPC		1.1
ClinPred		0.11	T
GERP RS		-0.47
Varity_R		0.12
gMVP		0.0048
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs768568016; hg19: chr19-58370408;