chr7-89335707-G-C

Variant names:

• chr7-89335707-G-C
• rs10487075
• NM_181646.5:c.2725G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF804B NM_181646.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 17 publications found

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

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=0.07489827).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181646.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804B	NM_181646.5	MANE Select	c.2725G>C	p.Glu909Gln	missense	Exon 4 of 4	NP_857597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804B	ENST00000333190.5	TSL:1 MANE Select	c.2725G>C	p.Glu909Gln	missense	Exon 4 of 4	ENSP00000329638.4
	ZNF804B	ENST00000611114.1	TSL:5	c.2476G>C	p.Glu826Gln	missense	Exon 3 of 3	ENSP00000478506.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.39
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.12
Sift	Uncertain	0.012	D
Sift4G	Benign	0.17	T
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
Mutation Taster		=98/2	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: rs10487075; hg19: chr7-88965021;