NM_001002836.4:c.775A>C

Variant names:

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

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>C​(p.Met259Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)
• Consequence: ZNF787 NM_001002836.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.059419155).

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>C	p.Met259Leu	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>C	p.Met259Leu	missense	Exon 3 of 3	ENSP00000478557.1	Q6DD87
	ZNF787	ENST00000969467.1		c.775A>C	p.Met259Leu	missense	Exon 3 of 3	ENSP00000639526.1
	ZNF787	ENST00000969468.1		c.775A>C	p.Met259Leu	missense	Exon 4 of 4	ENSP00000639527.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.24
DANN	Benign	0.36
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.68
PrimateAI	Pathogenic	0.87	D
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.46		Loss of MoRF binding (P = 0.0878)
MVP		0.043
ClinPred		0.022	T
GERP RS		-2.3
Varity_R		0.087
gMVP		0.23
Mutation Taster		=98/2	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;