7-89335707-G-C

Variant summary

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

The NM_181646.5(ZNF804B):c.2725G>C(p.Glu909Gln) 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. 14/21 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. E909K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF804B NM_181646.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07489827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF804B	NM_181646.5	c.2725G>C	p.Glu909Gln	missense_variant	4/4	ENST00000333190.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF804B	ENST00000333190.5	c.2725G>C	p.Glu909Gln	missense_variant	4/4	1	NM_181646.5	P1
ZNF804B	ENST00000611114.1	c.2476G>C	p.Glu826Gln	missense_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	15
Dann	Benign	0.94
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.95	N;.
REVEL	Benign	0.12
Sift	Uncertain	0.012	D;.
Sift4G	Benign	0.17	T;D
Polyphen		0.0090	B;.
Vest4		0.039
MutPred		0.070		Gain of catalytic residue at E909 (P = 0.0428);.;
MVP		0.061
MPC		0.040
ClinPred		0.087	T
GERP RS		2.0
Varity_R		0.092
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs10487075; hg19: chr7-88965021;