Variant chr12-8177369-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001004328.3(ZNF705A):c.689G>A(p.Cys230Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705A
NM_001004328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

Variant links:

Genes affected

ZNF705A (HGNC:32281): (zinc finger protein 705A) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF705A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705A	NM_001004328.3 linkuse as main transcript	c.689G>A	p.Cys230Tyr	missense_variant	6/6	ENST00000396570.8	NP_001004328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF705A	ENST00000396570.8 linkuse as main transcript	c.689G>A	p.Cys230Tyr	missense_variant	6/6	5	NM_001004328.3	ENSP00000379816	P1
ZNF705A	ENST00000359286.4 linkuse as main transcript	c.689G>A	p.Cys230Tyr	missense_variant	5/5	2		ENSP00000352233	P1
ZNF705A	ENST00000610508.4 linkuse as main transcript	c.689G>A	p.Cys230Tyr	missense_variant	6/6	5		ENSP00000481663	P1
ZNF705A	ENST00000398526.2 linkuse as main transcript	c.273+184G>A		intron_variant		3		ENSP00000475525

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1459710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726158

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:

0.00

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 23, 2023

The c.689G>A (p.C230Y) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a G to A substitution at nucleotide position 689, causing the cysteine (C) at amino acid position 230 to be replaced by a tyrosine (Y). 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

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

T;.

M_CAP

Benign

0.0051

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.45

MutationAssessor

Pathogenic

3.8

H;H

MutationTaster

Benign

0.65

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-11

.;D

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.46

MutPred

0.81

Loss of disorder (P = 0.0647);Loss of disorder (P = 0.0647);

MVP

0.92

MPC

2.5

ClinPred

0.79

GERP RS

1.4

Varity_R

0.76

gMVP

0.12

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.

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