Variant 16-30418197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000319296.10(ZNF771):c.784G>A(p.Ala262Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,351,896 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: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZNF771
ENST00000319296.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.02

Variant links:

Genes affected

ZNF771 (HGNC:29653): (zinc finger protein 771) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF771 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=0.028465033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF771	NM_001142305.2 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	3/3	ENST00000319296.10	NP_001135777.1
ZNF771	NM_016643.4 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	3/3		NP_057727.2
ZNF771	XM_047434196.1 linkuse as main transcript	c.859G>A	p.Ala287Thr	missense_variant	3/3		XP_047290152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF771	ENST00000319296.10 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	3/3	1	NM_001142305.2	ENSP00000323945	P1
ZNF771	ENST00000566625.2 linkuse as main transcript	c.141+10003G>A		intron_variant		1		ENSP00000460549
ZNF771	ENST00000434417.1 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	3/3	2		ENSP00000416197	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000962

AC:

AN:

1351896

Hom.:

Cov.:

AF XY:

0.00000751

AC XY:

AN XY:

665740

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:

0.0000103

Gnomad4 OTH exome

AF:

0.0000354

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 04, 2023

The c.784G>A (p.A262T) alteration is located in exon 3 (coding exon 2) of the ZNF771 gene. This alteration results from a G to A substitution at nucleotide position 784, causing the alanine (A) at amino acid position 262 to be replaced by a threonine (T). 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

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.3

DANN

Benign

0.95

DEOGEN2

Benign

0.0080

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.30

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.47

N;N

MutationTaster

Benign

0.99

D;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.65

N;N

REVEL

Benign

0.039

Sift

Benign

0.31

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.047

B;B

Vest4

0.042

MutPred

0.19

Gain of phosphorylation at A262 (P = 0.0287);Gain of phosphorylation at A262 (P = 0.0287);

MVP

0.31

MPC

1.7

ClinPred

0.24

GERP RS

-7.7

Varity_R

0.073

gMVP

0.086

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