chr19-56088388-C-T

Variant names:

• chr19-56088388-C-T
• rs1985426570
• NM_001002836.4:c.784G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001002836.4(ZNF787):​c.784G>A​(p.Ala262Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 958,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ZNF787 NM_001002836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0350
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059901506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002836.4. 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
	ZNF787	NM_001002836.4	MANE Select	c.784G>A	p.Ala262Thr	missense	Exon 3 of 3	NP_001002836.2	Q6DD87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF787	ENST00000610935.2	TSL:1 MANE Select	c.784G>A	p.Ala262Thr	missense	Exon 3 of 3	ENSP00000478557.1	Q6DD87
	ZNF787	ENST00000969467.1		c.784G>A	p.Ala262Thr	missense	Exon 3 of 3	ENSP00000639526.1
	ZNF787	ENST00000969468.1		c.784G>A	p.Ala262Thr	missense	Exon 4 of 4	ENSP00000639527.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000313 AC: 3 AN: 958132 Hom.: 0 Cov.: 33 AF XY: 0.00000222 AC XY: 1 AN XY: 450262

African (AFR) AF: 0.00 AC: 0 AN: 18194

American (AMR) AF: 0.00 AC: 0 AN: 4548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8674

East Asian (EAS) AF: 0.00 AC: 0 AN: 13814

South Asian (SAS) AF: 0.00 AC: 0 AN: 18748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2236

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 840996

Other (OTH) AF: 0.00 AC: 0 AN: 34650

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.9
DANN	Benign	0.93
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.035
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.41	T
Polyphen		0.0020	B
Vest4		0.050
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.043
ClinPred		0.044	T
GERP RS		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.019
gMVP		0.14
Mutation Taster		=99/1	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: rs1985426570; hg19: chr19-56599757;