10-62459537-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000395255.7(ZNF365):c.925-204C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,128 control chromosomes in the GnomAD database, including 4,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4643 hom., cov: 32)
• Consequence: ZNF365 ENST00000395255.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.119

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-62459537-C-A is Benign according to our data. Variant chr10-62459537-C-A is described in ClinVar as [Benign]. Clinvar id is 1275522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_199450.3	c.925-204C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395255.7	c.925-204C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31554 AN: 152010 Hom.: 4625 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.208 AC: 31600 AN: 152128 Hom.: 4643 Cov.: 32 AF XY: 0.207 AC XY: 15365 AN XY: 74382

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.180

Alfa AF: 0.174 Hom.: 394

Bravo AF: 0.220

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.8
Dann	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11818163; hg19: chr10-64219296;