Variant 15-34982473-T-C 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_014106.4(ZNF770):c.962A>G(p.Lys321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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

ZNF770
NM_014106.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

ZNF770 (HGNC:26061): (zinc finger protein 770) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF770 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=0.063727885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF770	NM_014106.4 link	c.962A>G	p.Lys321Arg	missense_variant	3/3	ENST00000356321.4	NP_054825.2	Q6IQ21
ZNF770	XM_011521744.4 link	c.962A>G	p.Lys321Arg	missense_variant	2/2		XP_011520046.1	Q6IQ21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF770	ENST00000356321.4 link	c.962A>G	p.Lys321Arg	missense_variant	3/3	1	NM_014106.4	ENSP00000348673.4		Q6IQ21

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249822

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461718

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

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

Apr 27, 2023

The c.962A>G (p.K321R) alteration is located in exon 3 (coding exon 1) of the ZNF770 gene. This alteration results from a A to G substitution at nucleotide position 962, causing the lysine (K) at amino acid position 321 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

0.094

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.66

M_CAP

Benign

0.0037

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.74

REVEL

Benign

0.080

Sift

Benign

0.36

Sift4G

Benign

0.39

Polyphen

0.012

Vest4

0.097

MutPred

0.41

Loss of methylation at K321 (P = 0.016);

MVP

0.068

MPC

0.097

ClinPred

0.036

GERP RS

3.8

Varity_R

0.028

gMVP

0.030

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