Genetic Variant ZNF365:n.611T>C (chr10-62399813-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000466727.1(ZNF365):n.611T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 1,596,674 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0074 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 75 hom. )

Consequence

ZNF365
ENST00000466727.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Publications

4 publications found

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:

ENSG00000285837 (HGNC:):

ENSG00000285837 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF365	NM_014951.3 link	c.*24T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000395254.8	NP_055766.2	Q70YC5-1
ZNF365	NM_199450.3 link	c.924+11237T>C		intron_variant	Intron 3 of 4		NP_955522.1	Q70YC5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF365	ENST00000466727.1 link	n.611T>C	non_coding_transcript_exon_variant	Exon 4 of 4	1
ZNF365	ENST00000395254.8 link	c.*24T>C	3_prime_UTR_variant	Exon 5 of 5	1	NM_014951.3	ENSP00000378674.3	Q70YC5-1
ENSG00000285837	ENST00000647733.1 link	c.924+11237T>C	intron_variant	Intron 3 of 7			ENSP00000502188.1
ZNF365	ENST00000395255.7 link	c.924+11237T>C	intron_variant	Intron 3 of 4	1		ENSP00000378675.3	Q70YC5-2

Frequencies

GnomAD3 genomes

AF:

0.00741

AC:

1127

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0237

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00754

AC:

1794

AN:

237980

AF XY:

0.00738

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.0000570

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00960

AC:

13864

AN:

1444410

Hom.:

Cov.:

AF XY:

0.00931

AC XY:

6664

AN XY:

716086

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

32734

American (AMR)

AF:

0.00248

AC:

106

AN:

42816

Ashkenazi Jewish (ASJ)

AF:

0.00463

AC:

119

AN:

25696

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39388

South Asian (SAS)

AF:

0.00234

AC:

199

AN:

85182

European-Finnish (FIN)

AF:

0.0205

AC:

1088

AN:

53050

Middle Eastern (MID)

AF:

0.00114

AC:

AN:

4378

European-Non Finnish (NFE)

AF:

0.0107

AC:

11761

AN:

1101728

Other (OTH)

AF:

0.00919

AC:

546

AN:

59438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

803

1605

2408

3210

4013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00740

AC:

1126

AN:

152264

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41548

American (AMR)

AF:

0.00346

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0237

AC:

251

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

703

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

114

172

229

286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00838

Hom.:

Bravo

AF:

0.00569

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

(source)

DANN

Benign

0.62

PhyloP100

-0.0010

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over