ZNF816 p.Lys622Asn

Variant names:

• chr19-52949909-C-A
• NM_001202457.3:c.1866G>T
• ZNF816 p.Lys622Asn

Your query was ambiguous. Multiple possible variants found:

• chr19-52949909-C-A
• chr19-52949909-C-G

Variant summary

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

The NM_001202457.3(ZNF816):​c.1866G>T​(p.Lys622Asn) 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. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF816 NM_001202457.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• Publications: 0 publications found

Genes affected

ZNF816 (HGNC:26995): (zinc finger protein 816) 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 integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF816-ZNF321P (HGNC:38879): (ZNF816-ZNF321P readthrough) This locus represents naturally occurring read-through transcription between the zinc finger protein 816 (ZNF816) gene and the zinc finger protein 321 (ZNF321) pseudogene on chromosome 19. The read-through transcript encodes a KRAB domain-containing protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus encoded by exon structure from the downstream pseudogene. [provided by RefSeq, Jan 2011]

ENSG00000306382 (HGNC:):

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=0.16645902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202457.3. 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
	ZNF816	NM_001202457.3	MANE Select	c.1866G>T	p.Lys622Asn	missense	Exon 4 of 4	NP_001189386.1	Q0VGE8
	ZNF816	NM_001031665.4		c.1866G>T	p.Lys622Asn	missense	Exon 5 of 5	NP_001026835.1	Q0VGE8
	ZNF816	NM_001202456.3		c.1866G>T	p.Lys622Asn	missense	Exon 4 of 4	NP_001189385.1	Q0VGE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF816	ENST00000444460.7	TSL:1 MANE Select	c.1866G>T	p.Lys622Asn	missense	Exon 4 of 4	ENSP00000403266.2	Q0VGE8
	ZNF816	ENST00000357666.8	TSL:1	c.1866G>T	p.Lys622Asn	missense	Exon 5 of 5	ENSP00000350295.4	Q0VGE8
	ZNF816-ZNF321P	ENST00000391777.3	TSL:2	c.190+2842G>T		intron	N/A	ENSP00000375656.3	A0A0X1KG74

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		-3.2
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.064
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.016	D
Varity_R		0.21
gMVP		0.010
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-53453162;