10-62376951-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014951.3(ZNF365):c.743+16_743+17del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,602,568 control chromosomes in the GnomAD database, including 68,047 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7225 hom., cov: 0)
  • Exomes 𝑓: 0.29 (60822 hom.)
• Consequence: ZNF365 NM_014951.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.684

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 -10 ACMG points.

• BP6: Variant 10-62376951-CAG-C is Benign according to our data. Variant chr10-62376951-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1257192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_014951.3	c.743+16_743+17del		intron_variant		ENST00000395254.8
ZNF365	NM_199450.3	c.743+16_743+17del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395254.8	c.743+16_743+17del		intron_variant		1	NM_014951.3	P1
ZNF365	ENST00000395255.7	c.743+16_743+17del		intron_variant		1
ZNF365	ENST00000466727.1	n.106+2494_106+2495del		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46066 AN: 151862 Hom.: 7223 Cov.: 0

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.289 AC: 69963 AN: 242244 Hom.: 10454 AF XY: 0.284 AC XY: 37371 AN XY: 131506

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.237

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.286 AC: 415026 AN: 1450588 Hom.: 60822 AF XY: 0.284 AC XY: 204433 AN XY: 720252

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.303 AC: 46103 AN: 151980 Hom.: 7225 Cov.: 0 AF XY: 0.299 AC XY: 22238 AN XY: 74306

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.324

Alfa AF: 0.305 Hom.: 1312

Bravo AF: 0.318

Asia WGS AF: 0.244 AC: 851 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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs149800343; hg19: chr10-64136710;