19-52553290-A-T

Position:

• chr19-52553290-A-T

Variant summary

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

The NM_001039886.4(ZNF808):​c.374A>T​(p.His125Leu) 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. 13/21 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: ZNF808 NM_001039886.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.526

Genes affected

ZNF808 (HGNC:33230): (zinc finger protein 808) Predicted to enable DNA-binding transcription activator 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]

ZNF808 (HGNC:):

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=0.15015674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF808	NM_001039886.4	c.374A>T	p.His125Leu	missense_variant	5/5	ENST00000359798.9	NP_001034975.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF808	ENST00000359798.9	c.374A>T	p.His125Leu	missense_variant	5/5	5	NM_001039886.4	ENSP00000352846.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 23, 2024

The c.374A>T (p.H125L) alteration is located in exon 5 (coding exon 3) of the ZNF808 gene. This alteration results from a A to T substitution at nucleotide position 374, causing the histidine (H) at amino acid position 125 to be replaced by a leucine (L). 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	0.079
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.7
DANN	Benign	0.67
DEOGEN2	Benign	0.037	T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.14	T;T;T;T
M_CAP	Benign	0.00076	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.5	M;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-6.5	D;D;D;D
REVEL	Benign	0.097
Sift	Benign	0.61	T;T;T;T
Sift4G	Benign	0.27	T;T;D;T
Polyphen		0.011	B;.;.;.
Vest4		0.13
MutPred		0.17		Loss of disorder (P = 0.1756);Loss of disorder (P = 0.1756);.;Loss of disorder (P = 0.1756);
MVP		0.45
MPC		0.12
ClinPred		0.19	T
GERP RS		-1.1
Varity_R		0.067
gMVP		0.018

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: chr19-53056543;