10-62376992-G-C

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.743+56G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,552,390 control chromosomes in the GnomAD database, including 767,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (71649 hom., cov: 32)
  • Exomes 𝑓: 1.0 (695831 hom.)
• Consequence: ZNF365 NM_014951.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.910

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=-0.95).
• BP6: Variant 10-62376992-G-C is Benign according to our data. Variant chr10-62376992-G-C is described in ClinVar as [Benign]. Clinvar id is 1178623.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.743+56G>C		intron_variant		ENST00000395254.8
ZNF365	NM_199450.3	c.743+56G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395254.8	c.743+56G>C		intron_variant		1	NM_014951.3	P1
ZNF365	ENST00000395255.7	c.743+56G>C		intron_variant		1
ZNF365	ENST00000466727.1	n.106+2534G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147431 AN: 152184 Hom.: 71596 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.977

GnomAD4 exome AF: 0.997 AC: 1395648 AN: 1400088 Hom.: 695831 AF XY: 0.997 AC XY: 688124 AN XY: 690026

Gnomad4 AFR exome AF: 0.884

Gnomad4 AMR exome AF: 0.995

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: 0.993

GnomAD4 genome AF: 0.969 AC: 147541 AN: 152302 Hom.: 71649 Cov.: 32 AF XY: 0.970 AC XY: 72236 AN XY: 74488

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.989

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.977

Alfa AF: 0.982 Hom.: 9127

Bravo AF: 0.964

Asia WGS AF: 0.995 AC: 3459 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	-0.95
Cadd	Benign	4.2
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1873686; hg19: chr10-64136751;