Variant chr8-80687419-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001033723.3(ZNF704):c.365C>T(p.Pro122Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,443,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF704
NM_001033723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

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:

ZNF704 (HGNC:):

ZNF704 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3597268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF704	NM_001033723.3 linkuse as main transcript	c.365C>T	p.Pro122Leu	missense_variant	4/9	ENST00000327835.7	NP_001028895.1	Q6ZNC4
ZNF704	NM_001367783.1 linkuse as main transcript	c.887C>T	p.Pro296Leu	missense_variant	4/9		NP_001354712.1
ZNF704	XM_017013725.2 linkuse as main transcript	c.389C>T	p.Pro130Leu	missense_variant	4/9		XP_016869214.1
ZNF704	XR_928797.3 linkuse as main transcript	n.1311C>T		non_coding_transcript_exon_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF704	ENST00000327835.7 linkuse as main transcript	c.365C>T	p.Pro122Leu	missense_variant	4/9	1	NM_001033723.3	ENSP00000331462.3	Q6ZNC4
ZNF704	ENST00000519936.2 linkuse as main transcript	c.887C>T	p.Pro296Leu	missense_variant	4/9	5		ENSP00000427715.2	E5RGL7
ZNF704	ENST00000520336.1 linkuse as main transcript	n.376C>T		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000136

AC:

AN:

220866

Hom.:

AF XY:

0.00000824

AC XY:

AN XY:

121386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000916

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1443150

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000690

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Dec 09, 2023

The c.365C>T (p.P122L) alteration is located in exon 4 (coding exon 3) of the ZNF704 gene. This alteration results from a C to T substitution at nucleotide position 365, causing the proline (P) at amino acid position 122 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.25

Sift

Benign

0.16

T;T

Sift4G

Benign

0.30

T;.

Polyphen

1.0

D;.

Vest4

0.72

MutPred

0.13

Loss of glycosylation at S127 (P = 0.0461);Loss of glycosylation at S127 (P = 0.0461);

MVP

0.17

MPC

1.4

ClinPred

0.76

GERP RS

5.7

Varity_R

0.13

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over