19-56088539-C-G

Position:

• chr19-56088539-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001002836.4(ZNF787):​c.633G>C​(p.Lys211Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000536 in 1,305,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: ZNF787 NM_001002836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.133

Genes affected

ZNF787 (HGNC:26998): (zinc finger protein 787) Enables sequence-specific double-stranded 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.

• PM1: In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZN787_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08191618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF787	NM_001002836.4	c.633G>C	p.Lys211Asn	missense_variant	3/3	ENST00000610935.2	NP_001002836.2
ZNF787	XM_047438164.1	c.633G>C	p.Lys211Asn	missense_variant	3/3		XP_047294120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF787	ENST00000610935.2	c.633G>C	p.Lys211Asn	missense_variant	3/3	1	NM_001002836.4	ENSP00000478557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000536 AC: 7 AN: 1305102 Hom.: 0 Cov.: 34 AF XY: 0.00000623 AC XY: 4 AN XY: 642322

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: 0.00000669

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Apr 21, 2022

The c.633G>C (p.K211N) alteration is located in exon 3 (coding exon 2) of the ZNF787 gene. This alteration results from a G to C substitution at nucleotide position 633, causing the lysine (K) at amino acid position 211 to be replaced by an asparagine (N). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.95	D
Sift4G	Benign	0.35	T
Polyphen		0.089	B
Vest4		0.18
MutPred		0.55		Loss of methylation at K211 (P = 0.0032);
MVP		0.043
ClinPred		0.056	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.15
gMVP		0.36

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: rs1985440358; hg19: chr19-56599908;