Variant chr10-62399574-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014951.3(ZNF365):c.1009G>T(p.Ala337Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,613,656 control chromosomes in the GnomAD database, including 280,486 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.47 ( 20323 hom., cov: 31)

Exomes 𝑓: 0.59 ( 260163 hom. )

Consequence

ZNF365
NM_014951.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.137

Variant links:

Genes affected

ZNF365 (HGNC:18194): (zinc finger protein 365) This gene encodes a zinc finger protein that may play a role in the repair of DNA damage and maintenance of genome stability. The N-terminal C2H2 zinc finger motif is required to form a protein complex with PARP1 and MRE11, which are known to be involved in the restart of stalled DNA replication forks. A mutation in this gene may be associated with breast cancer susceptibility. [provided by RefSeq, Mar 2020]

ZNF365 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-62399574-G-T is Benign according to our data. Variant chr10-62399574-G-T is described in ClinVar as [Benign]. Clinvar id is 1282011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_014951.3 linkuse as main transcript	c.1009G>T	p.Ala337Ser	missense_variant	5/5	ENST00000395254.8
ZNF365	NM_199450.3 linkuse as main transcript	c.924+10998G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395254.8 linkuse as main transcript	c.1009G>T	p.Ala337Ser	missense_variant	5/5	1	NM_014951.3	P1	Q70YC5-1
ZNF365	ENST00000395255.7 linkuse as main transcript	c.924+10998G>T		intron_variant		1			Q70YC5-2
ZNF365	ENST00000466727.1 linkuse as main transcript	n.372G>T		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71828

AN:

151706

Hom.:

20314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.553

AC:

138925

AN:

251404

Hom.:

40455

AF XY:

0.554

AC XY:

75266

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.693

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.608

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.590

AC:

862182

AN:

1461832

Hom.:

260163

Cov.:

AF XY:

0.587

AC XY:

427171

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.537

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.611

Gnomad4 NFE exome

AF:

0.616

Gnomad4 OTH exome

AF:

0.564

GnomAD4 genome

AF:

0.473

AC:

71837

AN:

151824

Hom.:

20323

Cov.:

AF XY:

0.474

AC XY:

35137

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.691

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.615

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.585

Hom.:

69211

Bravo

AF:

0.453

TwinsUK

AF:

0.612

AC:

2268

ALSPAC

AF:

0.615

AC:

2370

ESP6500AA

AF:

0.166

AC:

730

ESP6500EA

AF:

0.610

AC:

5250

ExAC

AF:

0.544

AC:

66081

Asia WGS

AF:

0.509

AC:

1767

AN:

3478

EpiCase

AF:

0.601

EpiControl

AF:

0.602

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	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.010

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0000018

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

0.48

REVEL

Benign

0.038

Sift

Benign

0.30

Sift4G

Benign

0.55

Polyphen

0.010

Vest4

0.012

ClinPred

0.0026

GERP RS

-1.9

Varity_R

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 18

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