8-80821408-C-T

Position:

• chr8-80821408-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033723.3(ZNF704):​c.187G>A​(p.Val63Ile) 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: ZNF704 NM_001033723.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

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]

ZNF704 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23263073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF704	NM_001033723.3	c.187G>A	p.Val63Ile	missense_variant	2/9	ENST00000327835.7	NP_001028895.1
ZNF704	NM_001367783.1	c.709G>A	p.Val237Ile	missense_variant	2/9		NP_001354712.1
ZNF704	XM_017013725.2	c.211G>A	p.Val71Ile	missense_variant	2/9		XP_016869214.1
ZNF704	XR_928797.3	n.1133G>A		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF704	ENST00000327835.7	c.187G>A	p.Val63Ile	missense_variant	2/9	1	NM_001033723.3	ENSP00000331462.3
ZNF704	ENST00000519936.2	c.709G>A	p.Val237Ile	missense_variant	2/9	5		ENSP00000427715.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.187G>A (p.V63I) alteration is located in exon 2 (coding exon 1) of the ZNF704 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the valine (V) at amino acid position 63 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.20
Sift	Benign	0.17	T;T
Sift4G	Benign	0.12	T;.
Polyphen		0.99	D;.
Vest4		0.41
MutPred		0.091		Loss of ubiquitination at K62 (P = 0.0394);Loss of ubiquitination at K62 (P = 0.0394);
MVP		0.068
MPC		1.1
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.089

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-81733643;