16-30555478-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001172679.2(ZNF764):​c.940T>C​(p.Tyr314His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF764 NM_001172679.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29834682).

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>C	p.Tyr314His	missense	Exon 3 of 3	NP_001166150.1	Q96H86-2
	ZNF764	NM_033410.4		c.943T>C	p.Tyr315His	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>C	p.Tyr314His	missense	Exon 3 of 3	ENSP00000378526.2	Q96H86-2
	ZNF764	ENST00000252797.6	TSL:1	c.943T>C	p.Tyr315His	missense	Exon 3 of 3	ENSP00000252797.2	Q96H86-1
	ZNF764	ENST00000952475.1		c.826T>C	p.Tyr276His	missense	Exon 2 of 2	ENSP00000622534.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.085	N
PhyloP100		3.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.28
Sift	Benign	0.032	D
Sift4G	Uncertain	0.047	D
Polyphen		0.70	P
Vest4		0.32
MutPred		0.48		Loss of phosphorylation at Y315 (P = 0.0333)
MVP		0.88
MPC		0.89
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.40
gMVP		0.41

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;