Genetic Variant NM_014951.3:c.743+180C>T (chr10-62377116-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014951.3(ZNF365):c.743+180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,094 control chromosomes in the GnomAD database, including 25,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 25001 hom., cov: 33)

Consequence

ZNF365
NM_014951.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.203

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 10-62377116-C-T is Benign according to our data. Variant chr10-62377116-C-T is described in ClinVar as Benign. ClinVar VariationId is 1274224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF365	NM_014951.3	MANE Select	c.743+180C>T		intron	N/A	NP_055766.2	Q70YC5-1
	ZNF365	NM_199450.3		c.743+180C>T		intron	N/A	NP_955522.1	Q70YC5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF365	ENST00000395254.8	TSL:1 MANE Select	c.743+180C>T	intron	N/A	ENSP00000378674.3	Q70YC5-1
ENSG00000285837	ENST00000647733.1		c.743+180C>T	intron	N/A	ENSP00000502188.1
ZNF365	ENST00000395255.7	TSL:1	c.743+180C>T	intron	N/A	ENSP00000378675.3	Q70YC5-2

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83544

AN:

151976

Hom.:

24999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.784

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.557

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.549

AC:

83566

AN:

152094

Hom.:

25001

Cov.:

AF XY:

0.554

AC XY:

41212

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.304

AC:

12620

AN:

41460

American (AMR)

AF:

0.570

AC:

8716

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2172

AN:

3468

East Asian (EAS)

AF:

0.784

AC:

4057

AN:

5174

South Asian (SAS)

AF:

0.659

AC:

3183

AN:

4830

European-Finnish (FIN)

AF:

0.684

AC:

7238

AN:

10588

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.644

AC:

43748

AN:

67968

Other (OTH)

AF:

0.558

AC:

1177

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1790

3580

5370

7160

8950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.604

Hom.:

35427

Bravo

AF:

0.526

Asia WGS

AF:

0.649

AC:

2252

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.0

(source)

DANN

Benign

0.55

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over