19-56088429-G-C

Position:

• chr19-56088429-G-C

Variant summary

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

The NM_001002836.4(ZNF787):​c.743C>G​(p.Ala248Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,042,614 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: 0.000016 (0 hom.)
• Consequence: ZNF787 NM_001002836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.380

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07578498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF787	NM_001002836.4	c.743C>G	p.Ala248Gly	missense_variant	3/3	ENST00000610935.2	NP_001002836.2
ZNF787	XM_047438164.1	c.743C>G	p.Ala248Gly	missense_variant	3/3		XP_047294120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF787	ENST00000610935.2	c.743C>G	p.Ala248Gly	missense_variant	3/3	1	NM_001002836.4	ENSP00000478557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000163 AC: 17 AN: 1042614 Hom.: 0 Cov.: 33 AF XY: 0.0000121 AC XY: 6 AN XY: 494472

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: 0.0000157

Gnomad4 OTH exome AF: 0.0000503

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 14, 2022

The c.743C>G (p.A248G) alteration is located in exon 3 (coding exon 2) of the ZNF787 gene. This alteration results from a C to G substitution at nucleotide position 743, causing the alanine (A) at amino acid position 248 to be replaced by a glycine (G). 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	Benign	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.87	D
Sift4G	Benign	0.19	T
Polyphen		0.057	B
Vest4		0.088
MutPred		0.33		Loss of stability (P = 0.1734);
MVP		0.043
ClinPred		0.13	T
GERP RS		2.6
Varity_R		0.077
gMVP		0.14

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: rs1167955551; hg19: chr19-56599798;