19-52553302-C-A

Variant names:

• chr19-52553302-C-A
• rs200197767
• NM_001039886.4:c.386C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039886.4(ZNF808):​c.386C>A​(p.Thr129Lys) 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. 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. T129M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF808 NM_001039886.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06967455).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039886.4. 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
	ZNF808	NM_001039886.4	MANE Select	c.386C>A	p.Thr129Lys	missense	Exon 5 of 5	NP_001034975.2	Q8N4W9-1
	ZNF808	NM_001321424.2		c.386C>A	p.Thr129Lys	missense	Exon 5 of 5	NP_001308353.1	Q8N4W9-1
	ZNF808	NM_001321425.2		c.386C>A	p.Thr129Lys	missense	Exon 4 of 4	NP_001308354.1	Q8N4W9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF808	ENST00000359798.9	TSL:5 MANE Select	c.386C>A	p.Thr129Lys	missense	Exon 5 of 5	ENSP00000352846.4	Q8N4W9-1
	ZNF808	ENST00000487863.5	TSL:1	n.179C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000420522.1	Q8N4W9-2
	ZNF808	ENST00000875424.1		c.386C>A	p.Thr129Lys	missense	Exon 4 of 4	ENSP00000545483.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.32
DANN	Benign	0.62
DEOGEN2	Benign	0.00032	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.017	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.46	N
PhyloP100		-2.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.025
Sift	Benign	0.091	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.43		Gain of ubiquitination at T129 (P = 0.0114)
MVP		0.19
MPC		0.12
ClinPred		0.054	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.022
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: rs200197767; hg19: chr19-53056555;