rs1985427983

Variant names:

• chr19-56088397-T-C
• rs1985427983
• NM_001002836.4:c.775A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-56088397-T-C
• chr19-56088397-T-A
• chr19-56088397-T-G

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.775A>G​(p.Met259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,099,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M259I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000071 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF787 NM_001002836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.680
• 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=0.057193547).

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.775A>G	p.Met259Val	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.775A>G	p.Met259Val	missense	Exon 3 of 3	ENSP00000478557.1	Q6DD87
	ZNF787	ENST00000969467.1		c.775A>G	p.Met259Val	missense	Exon 3 of 3	ENSP00000639526.1
	ZNF787	ENST00000969468.1		c.775A>G	p.Met259Val	missense	Exon 4 of 4	ENSP00000639527.1

Frequencies

GnomAD3 genomes AF: 0.00000705 AC: 1 AN: 141772 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000245

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 2 AN: 957908 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 450390

African (AFR) AF: 0.00 AC: 0 AN: 18276

American (AMR) AF: 0.000216 AC: 1 AN: 4638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8796

East Asian (EAS) AF: 0.00 AC: 0 AN: 14036

South Asian (SAS) AF: 0.00 AC: 0 AN: 18766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2250

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 840070

Other (OTH) AF: 0.00 AC: 0 AN: 34668

GnomAD4 genome AF: 0.00000705 AC: 1 AN: 141772 Hom.: 0 Cov.: 32 AF XY: 0.0000145 AC XY: 1 AN XY: 68904

African (AFR) AF: 0.00 AC: 0 AN: 39574

American (AMR) AF: 0.00 AC: 0 AN: 14312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.00 AC: 0 AN: 4330

South Asian (SAS) AF: 0.000245 AC: 1 AN: 4074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64924

Other (OTH) AF: 0.00 AC: 0 AN: 1984

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	0.064
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.1
DANN	Benign	0.50
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.68
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.41		Loss of solvent accessibility (P = 0.0111)
MVP		0.043
ClinPred		0.028	T
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.060
gMVP		0.30
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: rs1985427983; hg19: chr19-56599766;