chr8-80693016-C-G

Variant names:

• chr8-80693016-C-G
• rs145491398
• NM_001033723.3:c.313G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033723.3(ZNF704):​c.313G>C​(p.Val105Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF704 NM_001033723.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15041736).

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.313G>C	p.Val105Leu	missense	Exon 3 of 9	NP_001028895.1	Q6ZNC4
	ZNF704	NM_001367783.1		c.835G>C	p.Val279Leu	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.313G>C	p.Val105Leu	missense	Exon 3 of 9	ENSP00000331462.3	Q6ZNC4
	ZNF704	ENST00000519936.2	TSL:5	c.835G>C	p.Val279Leu	missense	Exon 3 of 9	ENSP00000427715.2	E5RGL7
	ZNF704	ENST00000520336.1	TSL:5	n.324G>C		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Benign	0.65	T
Polyphen		0.029	B
Vest4		0.40
MutPred		0.052		Gain of glycosylation at P104 (P = 0.0759)
MVP		0.068
MPC		0.78
ClinPred		0.65	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.36
Mutation Taster		=85/15	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: rs145491398; hg19: chr8-81605251;