chr16-30555478-A-C

Variant names:

• chr16-30555478-A-C
• rs2051542948
• NM_001172679.2:c.940T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001172679.2(ZNF764):​c.940T>G​(p.Tyr314Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,401,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y314H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF764 NM_001172679.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.940T>G	p.Tyr314Asp	missense	Exon 3 of 3	NP_001166150.1	Q96H86-2
	ZNF764	NM_033410.4		c.943T>G	p.Tyr315Asp	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.940T>G	p.Tyr314Asp	missense	Exon 3 of 3	ENSP00000378526.2	Q96H86-2
	ZNF764	ENST00000252797.6	TSL:1	c.943T>G	p.Tyr315Asp	missense	Exon 3 of 3	ENSP00000252797.2	Q96H86-1
	ZNF764	ENST00000952475.1		c.826T>G	p.Tyr276Asp	missense	Exon 2 of 2	ENSP00000622534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401608 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692672

African (AFR) AF: 0.00 AC: 0 AN: 31494

American (AMR) AF: 0.00 AC: 0 AN: 35784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22060

East Asian (EAS) AF: 0.00 AC: 0 AN: 38936

South Asian (SAS) AF: 0.00 AC: 0 AN: 76656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1086120

Other (OTH) AF: 0.00 AC: 0 AN: 57846

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	-0.077	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.9	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.52		Gain of ubiquitination at K313 (P = 0.0268)
MVP		0.90
MPC		1.0
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.91
gMVP		0.66
Mutation Taster		=96/4	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: rs2051542948; hg19: chr16-30566799;