rs202243737

chr19-56088086-C-Gchr19-56088086-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001002836.4(ZNF787):c.1086G>C(p.Glu362Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,486,494 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: ZNF787 NM_001002836.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -3.41

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002983451).
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF787	NM_001002836.4	c.1086G>C	p.Glu362Asp	missense_variant	3/3	ENST00000610935.2
ZNF787	XM_047438164.1	c.1086G>C	p.Glu362Asp	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF787	ENST00000610935.2	c.1086G>C	p.Glu362Asp	missense_variant	3/3	1	NM_001002836.4	P1

Frequencies

GnomAD3 genomes AF: 0.00455 AC: 678 AN: 148968 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00435

Gnomad ASJ AF: 0.00463

Gnomad EAS AF: 0.00218

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.0000993

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000607

Gnomad OTH AF: 0.00493

GnomAD3 exomes AF: 0.0000480 AC: 7 AN: 145912 Hom.: 0 AF XY: 0.0000357 AC XY: 3 AN XY: 84132

Gnomad AFR exome AF: 0.000473

Gnomad AMR exome AF: 0.0000473

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000117

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000293

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00126 AC: 1691 AN: 1337434 Hom.: 5 Cov.: 35 AF XY: 0.00121 AC XY: 806 AN XY: 664818

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00443

Gnomad4 EAS exome AF: 0.00194

Gnomad4 SAS exome AF: 0.000457

Gnomad4 FIN exome AF: 0.000183

Gnomad4 NFE exome AF: 0.000821

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.00456 AC: 680 AN: 149060 Hom.: 3 Cov.: 31 AF XY: 0.00434 AC XY: 315 AN XY: 72658

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.00435

Gnomad4 ASJ AF: 0.00463

Gnomad4 EAS AF: 0.00219

Gnomad4 SAS AF: 0.000420

Gnomad4 FIN AF: 0.0000993

Gnomad4 NFE AF: 0.000607

Gnomad4 OTH AF: 0.00488

Alfa AF: 0.000858 Hom.: 0

ExAC AF: 0.0000439 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum Uncertain:1

Uncertain significance, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.0040
Dann	Benign	0.86
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.87	D
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.36		Gain of helix (P = 0.062);
MVP		0.043
ClinPred		0.0094	T
GERP RS		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.034
gMVP		0.034

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: rs202243737; hg19: chr19-56599455; COSMIC: COSV54419955; COSMIC: COSV54419955;