chr19-57253381-C-G

Variant names:

• chr19-57253381-C-G
• rs750973544
• NM_001023563.4:c.562C>G

Variant summary

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

The NM_001023563.4(ZNF805):​c.562C>G​(p.His188Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,408,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. H188N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 0 publications found

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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=0.0677394).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023563.4. 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
	ZNF805	NM_001023563.4	MANE Select	c.562C>G	p.His188Asp	missense	Exon 4 of 4	NP_001018857.2	Q5CZA5-1
	ZNF805	NM_001145078.2		c.163C>G	p.His55Asp	missense	Exon 3 of 3	NP_001138550.1	Q5CZA5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF805	ENST00000414468.3	TSL:5 MANE Select	c.562C>G	p.His188Asp	missense	Exon 4 of 4	ENSP00000412999.1	Q5CZA5-1
	ZNF805	ENST00000354309.4	TSL:5	c.163C>G	p.His55Asp	missense	Exon 3 of 3	ENSP00000365414.2	Q5CZA5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000596 AC: 1 AN: 167678 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1408714 Hom.: 0 Cov.: 30 AF XY: 0.00000287 AC XY: 2 AN XY: 695906

African (AFR) AF: 0.00 AC: 0 AN: 31884

American (AMR) AF: 0.00 AC: 0 AN: 36498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25272

East Asian (EAS) AF: 0.00 AC: 0 AN: 36532

South Asian (SAS) AF: 0.00 AC: 0 AN: 80188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000369 AC: 4 AN: 1084080

Other (OTH) AF: 0.00 AC: 0 AN: 58440

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.1
DANN	Benign	0.77
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.023	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.31
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.025
Sift	Benign	0.21	T
Sift4G	Uncertain	0.053	T
Polyphen		0.078	B
Vest4		0.19
MutPred		0.44		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.068
MPC		0.35
ClinPred		0.024	T
GERP RS		-0.56
Varity_R		0.079
gMVP		0.017
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: rs750973544; hg19: chr19-57764749;