Variant chr7-64077750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001159522.3(ZNF727):c.701G>A(p.Gly234Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,431,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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: 0.0000042 ( 0 hom. )

Consequence

ZNF727
NM_001159522.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.46

Variant links:

Genes affected

ZNF727 (HGNC:22785): (zinc finger protein 727) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF727 links:

ZNF727 (HGNC:):

ZNF727 links:

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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=0.25765055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF727	NM_001159522.3 linkuse as main transcript	c.701G>A	p.Gly234Asp	missense_variant	4/4	ENST00000456806.3	NP_001152994.1	A8MUV8
ZNF727	XM_017012225.3 linkuse as main transcript	c.605G>A	p.Gly202Asp	missense_variant	3/3		XP_016867714.1
ZNF727	XR_242241.4 linkuse as main transcript	n.889G>A		non_coding_transcript_exon_variant	4/5
ZNF727	XR_927469.2 linkuse as main transcript	n.889G>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3 linkuse as main transcript	c.701G>A	p.Gly234Asp	missense_variant	4/4	4	NM_001159522.3	ENSP00000485448.1		A8MUV8
ENSG00000285544	ENST00000647787.1 linkuse as main transcript	n.197-17763G>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000419

AC:

AN:

1431548

Hom.:

Cov.:

AF XY:

0.00000564

AC XY:

AN XY:

709386

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:

0.00000547

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 08, 2022

The c.701G>A (p.G234D) alteration is located in exon 4 (coding exon 4) of the ZNF727 gene. This alteration results from a G to A substitution at nucleotide position 701, causing the glycine (G) at amino acid position 234 to be replaced by an aspartic acid (D). 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

0.33

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.20

M_CAP

Benign

0.0090

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.98

PrimateAI

Benign

0.35

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.23

MutPred

0.59

Gain of ubiquitination at K229 (P = 0.0325);

MVP

0.072

ClinPred

0.71

GERP RS

1.0

Varity_R

0.081

gMVP

0.014

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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