7-89333895-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.913G>C(p.Asp305His) 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: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF804B NM_181646.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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=0.12878448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF804B	NM_181646.5	c.913G>C	p.Asp305His	missense_variant	4/4	ENST00000333190.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF804B	ENST00000333190.5	c.913G>C	p.Asp305His	missense_variant	4/4	1	NM_181646.5	P1
ZNF804B	ENST00000611114.1	c.664G>C	p.Asp222His	missense_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000991 AC: 13 AN: 1311386 Hom.: 0 Cov.: 36 AF XY: 0.00000763 AC XY: 5 AN XY: 654994

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000485

Gnomad4 ASJ exome AF: 0.0000473

Gnomad4 EAS exome AF: 0.0000330

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000892

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 10, 2023

The c.913G>C (p.D305H) 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 913, causing the aspartic acid (D) at amino acid position 305 to be replaced by a histidine (H). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	D;.
REVEL	Benign	0.057
Sift	Uncertain	0.0030	D;.
Sift4G	Benign	0.10	T;D
Polyphen		0.99	D;.
Vest4		0.083
MutPred		0.22		Loss of helix (P = 0.0376);.;
MVP		0.41
MPC		0.045
ClinPred		0.86	D
GERP RS		2.4
Varity_R		0.13
gMVP		0.14

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: chr7-88963209;