chr19-52950000-G-C

Position:

• chr19-52950000-G-C

Variant summary

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

The NM_001202457.3(ZNF816):​c.1775C>G​(p.Pro592Arg) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF816 NM_001202457.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457

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:):

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=0.16484341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF816	NM_001202457.3	c.1775C>G	p.Pro592Arg	missense_variant	4/4	ENST00000444460.7	NP_001189386.1
ZNF816-ZNF321P	NM_001202473.2	c.190+2751C>G		intron_variant			NP_001189402.1
ZNF816	NM_001031665.4	c.1775C>G	p.Pro592Arg	missense_variant	5/5		NP_001026835.1
ZNF816	NM_001202456.3	c.1775C>G	p.Pro592Arg	missense_variant	4/4		NP_001189385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF816	ENST00000444460.7	c.1775C>G	p.Pro592Arg	missense_variant	4/4	1	NM_001202457.3	ENSP00000403266	P1
ZNF816	ENST00000357666.8	c.1775C>G	p.Pro592Arg	missense_variant	5/5	1		ENSP00000350295	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jan 23, 2023

The c.1775C>G (p.P592R) alteration is located in exon 5 (coding exon 3) of the ZNF816 gene. This alteration results from a C to G substitution at nucleotide position 1775, causing the proline (P) at amino acid position 592 to be replaced by an arginine (R). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.017	.;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.8	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.64	P;P
Vest4		0.29
MutPred		0.45		Gain of MoRF binding (P = 0.005);Gain of MoRF binding (P = 0.005);
MVP		0.27
MPC		0.45
ClinPred		0.84	D
GERP RS		1.8
Varity_R		0.21
gMVP		0.015

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: chr19-53453253;