Variant 12-8177099-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004328.3(ZNF705A):c.419G>T(p.Gly140Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,611,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF705A
NM_001004328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.726

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.117687106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705A	NM_001004328.3 linkuse as main transcript	c.419G>T	p.Gly140Val	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.419G>T	p.Gly140Val	missense_variant	6/6	5	NM_001004328.3	ENSP00000379816	P1
ZNF705A	ENST00000359286.4 linkuse as main transcript	c.419G>T	p.Gly140Val	missense_variant	5/5	2		ENSP00000352233	P1
ZNF705A	ENST00000610508.4 linkuse as main transcript	c.419G>T	p.Gly140Val	missense_variant	6/6	5		ENSP00000481663	P1
ZNF705A	ENST00000398526.2 linkuse as main transcript	c.188G>T	p.Gly63Val	missense_variant	2/3	3		ENSP00000475525

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

251068

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000867

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:

0.00000617

AC:

AN:

1459648

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726124

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0000671

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

AF:

0.000158

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000494

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

Jan 23, 2024

The c.419G>T (p.G140V) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a G to T substitution at nucleotide position 419, causing the glycine (G) at amino acid position 140 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.066

.;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.52

T;T;.

M_CAP

Benign

0.0041

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M;M

MutationTaster

Benign

0.97

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.6

D;.;D

REVEL

Benign

0.12

Sift

Benign

0.033

D;.;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.90

.;P;P

Vest4

0.15, 0.15

MVP

0.49

MPC

1.6

ClinPred

0.18

GERP RS

-2.7

Varity_R

0.11

gMVP

0.057

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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