Variant 12-8175931-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004328.3(ZNF705A):c.307A>G(p.Ser103Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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

ZNF705A
NM_001004328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.336

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06293595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705A	NM_001004328.3 linkuse as main transcript	c.307A>G	p.Ser103Gly	missense_variant	5/6	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.307A>G	p.Ser103Gly	missense_variant	5/6	5	NM_001004328.3	ENSP00000379816	P1
ZNF705A	ENST00000359286.4 linkuse as main transcript	c.307A>G	p.Ser103Gly	missense_variant	4/5	2		ENSP00000352233	P1
ZNF705A	ENST00000610508.4 linkuse as main transcript	c.307A>G	p.Ser103Gly	missense_variant	5/6	5		ENSP00000481663	P1
ZNF705A	ENST00000398526.2 linkuse as main transcript	c.76A>G	p.Ser26Gly	missense_variant	1/3	3		ENSP00000475525

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

230204

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

124924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000176

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:

0.00000206

AC:

AN:

1459194

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

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.:

ExAC

AF:

0.00000824

AC:

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

Aug 08, 2022

The c.307A>G (p.S103G) alteration is located in exon 4 (coding exon 4) of the ZNF705A gene. This alteration results from a A to G substitution at nucleotide position 307, causing the serine (S) at amino acid position 103 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.3

DANN

Benign

0.88

DEOGEN2

Benign

0.0011

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.24

T;T;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.99

.;L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.17

N;.;N

REVEL

Benign

0.011

Sift

Benign

0.36

T;.;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.070

.;B;B

Vest4

0.12, 0.12

MutPred

0.23

Loss of phosphorylation at S103 (P = 0.0405);Loss of phosphorylation at S103 (P = 0.0405);Loss of phosphorylation at S103 (P = 0.0405);

MVP

0.36

MPC

1.3

ClinPred

0.022

GERP RS

1.1

Varity_R

0.030

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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