Variant 8-37697800-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 ENST00000331569.6(ZNF703):c.899A>G(p.Lys300Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,530,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 1 hom. )

Consequence

ZNF703
ENST00000331569.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

ZNF703 (HGNC:25883): (zinc finger protein 703) Predicted to enable DNA-binding transcription factor binding activity. Involved in several processes, including cellular response to estradiol stimulus; mammary gland epithelial cell differentiation; and positive regulation of mammary gland epithelial cell proliferation. Located in cytoplasm and nuclear matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF703 links:

Genome browser will be placed here

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=0.008105904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF703	NM_025069.3 linkuse as main transcript	c.899A>G	p.Lys300Arg	missense_variant	2/2	ENST00000331569.6	NP_079345.1	Q9H7S9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF703	ENST00000331569.6 linkuse as main transcript	c.899A>G	p.Lys300Arg	missense_variant	2/2	1	NM_025069.3	ENSP00000332325.4		Q9H7S9

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00764

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00110

AC:

139

AN:

126482

Hom.:

AF XY:

0.00119

AC XY:

AN XY:

68974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000963

Gnomad FIN exome

AF:

0.00979

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000808

AC:

1114

AN:

1377972

Hom.:

Cov.:

AF XY:

0.000810

AC XY:

551

AN XY:

679882

show subpopulations

Gnomad4 AFR exome

AF:

0.0000326

Gnomad4 AMR exome

AF:

0.000283

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00941

Gnomad4 NFE exome

AF:

0.000612

Gnomad4 OTH exome

AF:

0.000641

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152202

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00764

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000934

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.000457

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

Jul 14, 2021

The c.899A>G (p.K300R) alteration is located in exon 2 (coding exon 2) of the ZNF703 gene. This alteration results from a A to G substitution at nucleotide position 899, causing the lysine (K) at amino acid position 300 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Benign

0.15

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.6

REVEL

Benign

0.11

Sift

Benign

0.070

Sift4G

Benign

0.20

Polyphen

0.94

Vest4

0.31

MutPred

0.18

Loss of ubiquitination at K300 (P = 0.0037);

MVP

0.56

ClinPred

0.048

GERP RS

3.2

Varity_R

0.16

gMVP

0.64

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

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