19-57253631-A-G

Position:

• chr19-57253631-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001023563.4(ZNF805):​c.812A>G​(p.Lys271Arg) 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. 15/21 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)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.559

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04078576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF805	NM_001023563.4	c.812A>G	p.Lys271Arg	missense_variant	4/4	ENST00000414468.3	NP_001018857.2
ZNF805	NM_001145078.2	c.413A>G	p.Lys138Arg	missense_variant	3/3		NP_001138550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF805	ENST00000414468.3	c.812A>G	p.Lys271Arg	missense_variant	4/4	5	NM_001023563.4	ENSP00000412999	P1
ZNF805	ENST00000354309.4	c.413A>G	p.Lys138Arg	missense_variant	3/3	5		ENSP00000365414

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 96

GnomAD4 genome Cov.: 32

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

Jun 23, 2023

The c.812A>G (p.K271R) alteration is located in exon 4 (coding exon 4) of the ZNF805 gene. This alteration results from a A to G substitution at nucleotide position 812, causing the lysine (K) at amino acid position 271 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.081
DEOGEN2	Benign	0.00092	.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.026
Sift	Benign	1.0	T;T
Sift4G	Benign	0.85	T;T
Polyphen		0.0010	.;B
Vest4		0.058
MutPred		0.41		.;Loss of methylation at K271 (P = 0.0159);
MVP		0.082
MPC		0.21
ClinPred		0.027	T
GERP RS		2.2
Varity_R		0.045
gMVP		0.011

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57764999;