Variant 8-80693051-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001033723.3(ZNF704):c.278G>C(p.Ser93Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF704
NM_001033723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.32

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF704	NM_001033723.3 linkuse as main transcript	c.278G>C	p.Ser93Thr	missense_variant	3/9	ENST00000327835.7	NP_001028895.1
ZNF704	NM_001367783.1 linkuse as main transcript	c.800G>C	p.Ser267Thr	missense_variant	3/9		NP_001354712.1
ZNF704	XM_017013725.2 linkuse as main transcript	c.302G>C	p.Ser101Thr	missense_variant	3/9		XP_016869214.1
ZNF704	XR_928797.3 linkuse as main transcript	n.1224G>C		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF704	ENST00000327835.7 linkuse as main transcript	c.278G>C	p.Ser93Thr	missense_variant	3/9	1	NM_001033723.3	ENSP00000331462	P1
ZNF704	ENST00000519936.2 linkuse as main transcript	c.800G>C	p.Ser267Thr	missense_variant	3/9	5		ENSP00000427715
ZNF704	ENST00000520336.1 linkuse as main transcript	n.289G>C		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.278G>C (p.S93T) alteration is located in exon 3 (coding exon 2) of the ZNF704 gene. This alteration results from a G to C substitution at nucleotide position 278, causing the serine (S) at amino acid position 93 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.18

Sift

Benign

0.033

D;D

Sift4G

Benign

0.073

T;.

Polyphen

0.97

D;.

Vest4

0.91

MutPred

0.26

Loss of phosphorylation at S93 (P = 0.0779);Loss of phosphorylation at S93 (P = 0.0779);

MVP

0.25

MPC

0.57

ClinPred

0.97

GERP RS

5.3

Varity_R

0.52

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over