NM_181646.5:c.2725G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181646.5(ZNF804B):​c.2725G>A​(p.Glu909Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 1,613,950 control chromosomes in the GnomAD database, including 8,100 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.074 (551 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7549 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020000637).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

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>A	p.Glu909Lys	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>A	p.Glu909Lys	missense	Exon 4 of 4	ENSP00000329638.4
	ZNF804B	ENST00000611114.1	TSL:5	c.2476G>A	p.Glu826Lys	missense	Exon 3 of 3	ENSP00000478506.1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11326 AN: 152066 Hom.: 550 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0755

GnomAD2 exomes AF: 0.0819 AC: 20570 AN: 251288 AF XY: 0.0836

Gnomad AFR exome AF: 0.0171

Gnomad AMR exome AF: 0.0401

Gnomad ASJ exome AF: 0.0855

Gnomad EAS exome AF: 0.0589

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0930

GnomAD4 exome AF: 0.0982 AC: 143476 AN: 1461766 Hom.: 7549 Cov.: 38 AF XY: 0.0969 AC XY: 70486 AN XY: 727186

African (AFR) AF: 0.0142 AC: 476 AN: 33468

American (AMR) AF: 0.0415 AC: 1855 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 2167 AN: 26122

East Asian (EAS) AF: 0.0724 AC: 2873 AN: 39696

South Asian (SAS) AF: 0.0586 AC: 5057 AN: 86258

European-Finnish (FIN) AF: 0.131 AC: 6997 AN: 53420

Middle Eastern (MID) AF: 0.0905 AC: 522 AN: 5768

European-Non Finnish (NFE) AF: 0.106 AC: 118026 AN: 1111934

Other (OTH) AF: 0.0911 AC: 5503 AN: 60396

GnomAD4 genome AF: 0.0744 AC: 11330 AN: 152184 Hom.: 551 Cov.: 32 AF XY: 0.0742 AC XY: 5522 AN XY: 74388

African (AFR) AF: 0.0178 AC: 740 AN: 41546

American (AMR) AF: 0.0543 AC: 829 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.0633 AC: 326 AN: 5150

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4824

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10584

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7282 AN: 68020

Other (OTH) AF: 0.0775 AC: 164 AN: 2116

Alfa AF: 0.0929 Hom.: 1899

Bravo AF: 0.0660

TwinsUK AF: 0.103 AC: 381

ALSPAC AF: 0.114 AC: 439

ESP6500AA AF: 0.0238 AC: 105

ESP6500EA AF: 0.107 AC: 917

ExAC AF: 0.0812 AC: 9863

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.39
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.10
Sift	Uncertain	0.011	D
Sift4G	Benign	0.087	T
Polyphen		0.0020	B
Vest4		0.027
MPC		0.048
ClinPred		0.0033	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.17
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV107358385;