16-30555460-C-A

Variant names:

• chr16-30555460-C-A
• rs919473844
• NM_001172679.2:c.958G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001172679.2(ZNF764):​c.958G>T​(p.Gly320Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G320R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF764 NM_001172679.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

Genes affected

ZNF764 (HGNC:28200): (zinc finger protein 764) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172679.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF764	NM_001172679.2	MANE Select	c.958G>T	p.Gly320Trp	missense	Exon 3 of 3	NP_001166150.1	Q96H86-2
	ZNF764	NM_033410.4		c.961G>T	p.Gly321Trp	missense	Exon 3 of 3	NP_219363.2	Q96H86-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF764	ENST00000395091.3	TSL:2 MANE Select	c.958G>T	p.Gly320Trp	missense	Exon 3 of 3	ENSP00000378526.2	Q96H86-2
	ZNF764	ENST00000252797.6	TSL:1	c.961G>T	p.Gly321Trp	missense	Exon 3 of 3	ENSP00000252797.2	Q96H86-1
	ZNF764	ENST00000952475.1		c.844G>T	p.Gly282Trp	missense	Exon 2 of 2	ENSP00000622534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394414 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689840

African (AFR) AF: 0.00 AC: 0 AN: 31728

American (AMR) AF: 0.00 AC: 0 AN: 37194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22654

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38850

South Asian (SAS) AF: 0.00 AC: 0 AN: 77686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075298

Other (OTH) AF: 0.00 AC: 0 AN: 57644

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.61		Gain of catalytic residue at G321 (P = 0.0508)
MVP		0.76
MPC		0.85
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.91
gMVP		0.33

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: rs919473844; hg19: chr16-30566781;