10-62388366-C-A

Variant summary

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

The NM_014951.3(ZNF365):c.744-30C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,586 control chromosomes in the GnomAD database, including 791,771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68610 hom., cov: 32)
  • Exomes 𝑓: 0.99 (723161 hom.)
• Consequence: ZNF365 NM_014951.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.40

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=-0.88).
• BP6: Variant 10-62388366-C-A is Benign according to our data. Variant chr10-62388366-C-A is described in ClinVar as [Benign]. Clinvar id is 1271699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_014951.3	c.744-30C>A		intron_variant		ENST00000395254.8
ZNF365	NM_199450.3	c.744-30C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395254.8	c.744-30C>A		intron_variant		1	NM_014951.3	P1
ZNF365	ENST00000395255.7	c.744-30C>A		intron_variant		1
ZNF365	ENST00000466727.1	n.107-30C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143927 AN: 152138 Hom.: 68579 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.962

GnomAD3 exomes AF: 0.986 AC: 247342 AN: 250880 Hom.: 122198 AF XY: 0.990 AC XY: 134261 AN XY: 135634

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.994 AC: 1453089 AN: 1461330 Hom.: 723161 Cov.: 40 AF XY: 0.995 AC XY: 723413 AN XY: 726912

Gnomad4 AFR exome AF: 0.799

Gnomad4 AMR exome AF: 0.990

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.987

GnomAD4 genome AF: 0.946 AC: 144008 AN: 152256 Hom.: 68610 Cov.: 32 AF XY: 0.948 AC XY: 70570 AN XY: 74460

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.962

Alfa AF: 0.969 Hom.: 10211

Bravo AF: 0.938

Asia WGS AF: 0.989 AC: 3439 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.15
Dann	Benign	0.63

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: rs3852424; hg19: chr10-64148125;