Variant 16-30418119-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001142305.2(ZNF771):c.706T>C(p.Cys236Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000753 in 1,328,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

ZNF771
NM_001142305.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF771	NM_001142305.2 link	c.706T>C	p.Cys236Arg	missense_variant	3/3	ENST00000319296.10	NP_001135777.1	Q7L3S4B2R9V3
ZNF771	NM_016643.4 link	c.706T>C	p.Cys236Arg	missense_variant	3/3		NP_057727.2	Q7L3S4B2R9V3
ZNF771	XM_047434196.1 link	c.781T>C	p.Cys261Arg	missense_variant	3/3		XP_047290152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF771	ENST00000319296.10 link	c.706T>C	p.Cys236Arg	missense_variant	3/3	1	NM_001142305.2	ENSP00000323945.5	Q7L3S4
ZNF771	ENST00000566625.2 link	c.141+9925T>C		intron_variant		1		ENSP00000460549.1	I3L3L5
ZNF771	ENST00000434417.1 link	c.706T>C	p.Cys236Arg	missense_variant	3/3	2		ENSP00000416197.1	Q7L3S4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.53e-7

AC:

AN:

1328684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654026

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:

9.48e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Mar 01, 2024

The c.706T>C (p.C236R) alteration is located in exon 3 (coding exon 2) of the ZNF771 gene. This alteration results from a T to C substitution at nucleotide position 706, causing the cysteine (C) at amino acid position 236 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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.52

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;D

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

.;T

M_CAP

Pathogenic

0.69

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Pathogenic

0.86

MutationAssessor

Pathogenic

4.6

H;H

PrimateAI

Pathogenic

0.98

PROVEAN

Pathogenic

-12

D;D

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.79

MVP

0.98

MPC

4.9

ClinPred

1.0

GERP RS

5.0

Varity_R

0.98

gMVP

0.71

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