7-89333491-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181646.5(ZNF804B):c.509G>C(p.Gly170Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 151,818 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: 32)
• Consequence: ZNF804B NM_181646.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

Genes affected

ZNF804B (HGNC:21958): (zinc finger protein 804B) Predicted to enable metal ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2966137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF804B	NM_181646.5	c.509G>C	p.Gly170Ala	missense_variant	4/4	ENST00000333190.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF804B	ENST00000333190.5	c.509G>C	p.Gly170Ala	missense_variant	4/4	1	NM_181646.5	P1
ZNF804B	ENST00000611114.1	c.260G>C	p.Gly87Ala	missense_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151818 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151818 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74126

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

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

Apr 13, 2023

The c.509G>C (p.G170A) alteration is located in exon 4 (coding exon 4) of the ZNF804B gene. This alteration results from a G to C substitution at nucleotide position 509, causing the glycine (G) at amino acid position 170 to be replaced by an alanine (A). 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	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0082	T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.2	N;.
REVEL	Benign	0.15
Sift	Benign	0.053	T;.
Sift4G	Uncertain	0.029	D;D
Polyphen		1.0	D;.
Vest4		0.44
MVP		0.26
MPC		0.28
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1172168545; hg19: chr7-88962805;