chr8-80693070-C-T

Variant names:

• chr8-80693070-C-T
• NM_001033723.3:c.259G>A

Variant summary

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

The NM_001033723.3(ZNF704):​c.259G>A​(p.Ala87Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF704 NM_001033723.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32
• Publications: 0 publications found

Genes affected

ZNF704 (HGNC:32291): (zinc finger protein 704) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000296763 (HGNC:):

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_001033723.3. 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
	ZNF704	NM_001033723.3	MANE Select	c.259G>A	p.Ala87Thr	missense	Exon 3 of 9	NP_001028895.1	Q6ZNC4
	ZNF704	NM_001367783.1		c.781G>A	p.Ala261Thr	missense	Exon 3 of 9	NP_001354712.1	E5RGL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF704	ENST00000327835.7	TSL:1 MANE Select	c.259G>A	p.Ala87Thr	missense	Exon 3 of 9	ENSP00000331462.3	Q6ZNC4
	ZNF704	ENST00000519936.2	TSL:5	c.781G>A	p.Ala261Thr	missense	Exon 3 of 9	ENSP00000427715.2	E5RGL7
	ZNF704	ENST00000520336.1	TSL:5	n.270G>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.36		Gain of glycosylation at A87 (P = 0.0349)
MVP		0.64
MPC		1.3
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.79
gMVP		0.72
Mutation Taster		=34/66	disease causing

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

hg19: chr8-81605305;