10-62479950-A-G

Variant summary

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

The ENST00000395255.7(ZNF365):c.*54A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,609,644 control chromosomes in the GnomAD database, including 2,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (314 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2482 hom.)
• Consequence: ZNF365 ENST00000395255.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.467

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=-0.94).
• BP6: Variant 10-62479950-A-G is Benign according to our data. Variant chr10-62479950-A-G is described in ClinVar as [Benign]. Clinvar id is 1269068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_199450.3	c.*54A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395255.7	c.*54A>G		3_prime_UTR_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9246 AN: 152146 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0482

GnomAD4 exome AF: 0.0539 AC: 78534 AN: 1457380 Hom.: 2482 Cov.: 30 AF XY: 0.0538 AC XY: 39012 AN XY: 724918

Gnomad4 AFR exome AF: 0.0689

Gnomad4 AMR exome AF: 0.0561

Gnomad4 ASJ exome AF: 0.0387

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.0514

Gnomad4 FIN exome AF: 0.0513

Gnomad4 NFE exome AF: 0.0504

Gnomad4 OTH exome AF: 0.0529

GnomAD4 genome AF: 0.0608 AC: 9258 AN: 152264 Hom.: 314 Cov.: 32 AF XY: 0.0608 AC XY: 4525 AN XY: 74446

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0568

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0525

Gnomad4 OTH AF: 0.0496

Alfa AF: 0.0503 Hom.: 193

Bravo AF: 0.0623

Asia WGS AF: 0.115 AC: 399 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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.44
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11819488; hg19: chr10-64239709; COSMIC: COSV67926936;