Variant 10-62388366-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014951.3(ZNF365):c.744-30C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,586 control chromosomes in the GnomAD database, including 791,771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68610 hom., cov: 32)

Exomes 𝑓: 0.99 ( 723161 hom. )

Consequence

ZNF365
NM_014951.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.40

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-62388366-C-A is Benign according to our data. Variant chr10-62388366-C-A is described in ClinVar as [Benign]. Clinvar id is 1271699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF365	NM_014951.3 linkuse as main transcript	c.744-30C>A		intron_variant		ENST00000395254.8	NP_055766.2
ZNF365	NM_199450.3 linkuse as main transcript	c.744-30C>A		intron_variant			NP_955522.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ZNF365	ENST00000395254.8 linkuse as main transcript	c.744-30C>A	intron_variant	1	NM_014951.3	ENSP00000378674	P1	Q70YC5-1
ZNF365	ENST00000395255.7 linkuse as main transcript	c.744-30C>A	intron_variant	1		ENSP00000378675		Q70YC5-2
ZNF365	ENST00000466727.1 linkuse as main transcript	n.107-30C>A	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.946

AC:

143927

AN:

152138

Hom.:

68579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.812

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.980

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.962

GnomAD3 exomes

AF:

0.986

AC:

247342

AN:

250880

Hom.:

122198

AF XY:

0.990

AC XY:

134261

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.805

Gnomad AMR exome

AF:

0.991

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.994

AC:

1453089

AN:

1461330

Hom.:

723161

Cov.:

AF XY:

0.995

AC XY:

723413

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.799

Gnomad4 AMR exome

AF:

0.990

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.987

GnomAD4 genome

AF:

0.946

AC:

144008

AN:

152256

Hom.:

68610

Cov.:

AF XY:

0.948

AC XY:

70570

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.812

Gnomad4 AMR

AF:

0.980

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.962

Alfa

AF:

0.969

Hom.:

10211

Bravo

AF:

0.938

Asia WGS

AF:

0.989

AC:

3439

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	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.15

DANN

Benign

0.63

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