Variant 7-64077296-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001159522.3(ZNF727):c.247G>A(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,526,378 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 31 hom. )

Consequence

ZNF727
NM_001159522.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.276

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:

ENSG00000285544 (HGNC:):

ENSG00000285544 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025950074).

BP6

Variant 7-64077296-G-A is Benign according to our data. Variant chr7-64077296-G-A is described in ClinVar as [Benign]. Clinvar id is 712646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1893/150858) while in subpopulation AFR AF= 0.042 (1723/41046). AF 95% confidence interval is 0.0403. There are 49 homozygotes in gnomad4. There are 886 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF727	NM_001159522.3 link	c.247G>A	p.Ala83Thr	missense_variant	4/4	ENST00000456806.3	NP_001152994.1	A8MUV8
ZNF727	XM_017012225.3 link	c.151G>A	p.Ala51Thr	missense_variant	3/3		XP_016867714.1
ZNF727	XR_242241.4 link	n.435G>A		non_coding_transcript_exon_variant	4/5
ZNF727	XR_927469.2 link	n.435G>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3 link	c.247G>A	p.Ala83Thr	missense_variant	4/4	4	NM_001159522.3	ENSP00000485448.1		A8MUV8
ENSG00000285544	ENST00000647787.1 link	n.197-18217G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1891

AN:

150748

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00723

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000975

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000575

Gnomad OTH

AF:

0.00824

GnomAD3 exomes

AF:

0.00308

AC:

432

AN:

140058

Hom.:

AF XY:

0.00239

AC XY:

178

AN XY:

74446

show subpopulations

Gnomad AFR exome

AF:

0.0410

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000504

Gnomad FIN exome

AF:

0.000123

Gnomad NFE exome

AF:

0.000740

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00150

AC:

2061

AN:

1375520

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

915

AN XY:

676872

show subpopulations

Gnomad4 AFR exome

AF:

0.0398

Gnomad4 AMR exome

AF:

0.00410

Gnomad4 ASJ exome

AF:

0.0000416

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.000102

Gnomad4 NFE exome

AF:

0.000440

Gnomad4 OTH exome

AF:

0.00382

GnomAD4 genome

AF:

0.0125

AC:

1893

AN:

150858

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

886

AN XY:

73576

show subpopulations

Gnomad4 AFR

AF:

0.0420

Gnomad4 AMR

AF:

0.00722

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000975

Gnomad4 NFE

AF:

0.000575

Gnomad4 OTH

AF:

0.00817

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.0142

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0434

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.00410

AC:

100

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.9

DANN

Benign

0.93

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00034

LIST_S2

Benign

0.095

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.23

Sift4G

Benign

0.17

Polyphen

0.90

Vest4

0.072

MVP

0.014

ClinPred

0.0091

GERP RS

-0.32

Varity_R

0.020

gMVP

0.023

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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