19-52553121-C-A

Variant names:

• chr19-52553121-C-A
• rs767168483
• NM_001039886.4:c.205C>A

Variant summary

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

The NM_001039886.4(ZNF808):​c.205C>A​(p.His69Asn) 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. H69R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF808 NM_001039886.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• 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=0.044296622).

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.205C>A	p.His69Asn	missense	Exon 5 of 5	NP_001034975.2	Q8N4W9-1
	ZNF808	NM_001321424.2		c.205C>A	p.His69Asn	missense	Exon 5 of 5	NP_001308353.1	Q8N4W9-1
	ZNF808	NM_001321425.2		c.205C>A	p.His69Asn	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.205C>A	p.His69Asn	missense	Exon 5 of 5	ENSP00000352846.4	Q8N4W9-1
	ZNF808	ENST00000487863.5	TSL:1	n.-3C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000420522.1	Q8N4W9-2
	ZNF808	ENST00000487863.5	TSL:1	n.-3C>A		5_prime_UTR	Exon 3 of 4	ENSP00000420522.1	Q8N4W9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 206190 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

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	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.077
DANN	Benign	0.38
DEOGEN2	Benign	0.00028	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.024	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.32	N
PhyloP100		-1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.034
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.0060	B
Vest4		0.064
MutPred		0.41		Gain of loop (P = 0.024)
MVP		0.11
MPC		0.11
ClinPred		0.041	T
GERP RS		-2.0
Varity_R		0.040
gMVP		0.013
Mutation Taster		=97/3	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: rs767168483; hg19: chr19-53056374;