19-52543291-C-T

Variant names:

• chr19-52543291-C-T
• rs571730362
• NM_001039886.4:c.7C>T

Variant summary

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

The NM_001363550.2(ZNF808):​c.-74C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: ZNF808 NM_001363550.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.124
• Publications: 0 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: 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=0.046595633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363550.2. 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.7C>T	p.Arg3Cys	missense	Exon 3 of 5	NP_001034975.2	Q8N4W9-1
	ZNF808	NM_001363550.2		c.-74C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001350479.1	Q8N4W9-2
	ZNF808	NM_001321424.2		c.7C>T	p.Arg3Cys	missense	Exon 3 of 5	NP_001308353.1	Q8N4W9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF808	ENST00000359798.9	TSL:5 MANE Select	c.7C>T	p.Arg3Cys	missense	Exon 3 of 5	ENSP00000352846.4	Q8N4W9-1
	ZNF808	ENST00000487863.5	TSL:1	n.-74C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000420522.1	Q8N4W9-2
	ZNF808	ENST00000487863.5	TSL:1	n.-74C>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000420522.1	Q8N4W9-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 251014 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000746 AC: 109 AN: 1461430 Hom.: 0 Cov.: 30 AF XY: 0.0000756 AC XY: 55 AN XY: 727050

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.0000447 AC: 2 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000882 AC: 98 AN: 1111740

Other (OTH) AF: 0.0000994 AC: 6 AN: 60362

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151948 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74188

African (AFR) AF: 0.0000242 AC: 1 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000314 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.12
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.072	T
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.19
MVP		0.13
MPC		0.13
ClinPred		0.053	T
GERP RS		-1.1
Varity_R		0.051
gMVP		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs571730362; hg19: chr19-53046544;