rs763707921

Variant names:

• chr19-57858849-A-C
• rs763707921
• NM_032828.4:c.437A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-57858849-A-C
• chr19-57858849-A-G

Variant summary

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

The NM_032828.4(ZNF587):​c.437A>C​(p.Lys146Thr) 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. 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. K146R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 26)
• Consequence: ZNF587 NM_032828.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

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=0.14372945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF587	NM_032828.4	c.437A>C	p.Lys146Thr	missense_variant	Exon 3 of 3	ENST00000339656.8	NP_116217.1
ZNF587	NM_001204817.2	c.434A>C	p.Lys145Thr	missense_variant	Exon 3 of 3		NP_001191746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF587	ENST00000339656.8	c.437A>C	p.Lys146Thr	missense_variant	Exon 3 of 3	1	NM_032828.4	ENSP00000345479.4
ENSG00000268750	ENST00000593873.6	c.*79A>C		3_prime_UTR_variant	Exon 2 of 2	4		ENSP00000469133.2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	.;.;.;T;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.38	.;T;T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.5	.;.;.;H;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.4	.;.;.;D;D;D
REVEL	Benign	0.017
Sift	Uncertain	0.019	.;.;.;D;D;D
Sift4G	Uncertain	0.015	D;D;T;D;D;D
Polyphen		0.98	.;.;.;D;.;.
Vest4		0.15, 0.18, 0.15
MutPred		0.40		.;.;Loss of methylation at K146 (P = 2e-04);Loss of methylation at K146 (P = 2e-04);.;.;
MVP		0.12
MPC		1.8
ClinPred		0.89	D
GERP RS		1.4
Varity_R		0.22
gMVP		0.011

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

LitVar

Other links and lift over

dbSNP: rs763707921; hg19: chr19-58370217;