Genetic Variant ZNF705A:p.Gln173Lys (chr12-8177197-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001004328.3(ZNF705A):c.517C>A(p.Gln173Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,848 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZNF705A
NM_001004328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.00

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=0.13697037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF705A	NM_001004328.3 link	c.517C>A	p.Gln173Lys	missense_variant	Exon 6 of 6	ENST00000396570.8	NP_001004328.1	Q6ZN79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF705A	ENST00000396570.8 link	c.517C>A	p.Gln173Lys	missense_variant	Exon 6 of 6	5	NM_001004328.3	ENSP00000379816.4	Q6ZN79J3KPU9
ZNF705A	ENST00000359286.4 link	c.517C>A	p.Gln173Lys	missense_variant	Exon 5 of 5	2		ENSP00000352233.4	Q6ZN79
ZNF705A	ENST00000610508.4 link	c.517C>A	p.Gln173Lys	missense_variant	Exon 6 of 6	5		ENSP00000481663.1	Q6ZN79
ZNF705A	ENST00000398526.2 link	c.271+12C>A		intron_variant	Intron 2 of 2	3		ENSP00000475525.1	U3KQ42

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250884

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1459680

Hom.:

Cov.:

102

AF XY:

0.0000165

AC XY:

AN XY:

726136

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.517C>A (p.Q173K) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a C to A substitution at nucleotide position 517, causing the glutamine (Q) at amino acid position 173 to be replaced by a lysine (K). 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

0.066

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.62

DANN

Benign

0.65

DEOGEN2

Benign

0.00011

.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.056

T;T;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.34

.;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.31

N;.;N

REVEL

Benign

0.019

Sift

Benign

0.081

T;.;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0070

.;B;B

Vest4

0.077, 0.076

MutPred

0.36

Gain of methylation at Q173 (P = 2e-04);Gain of methylation at Q173 (P = 2e-04);Gain of methylation at Q173 (P = 2e-04);

MVP

0.26

MPC

1.6

ClinPred

0.055

GERP RS

0.38

Varity_R

0.047

gMVP

0.020

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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