10-62377116-C-T

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+180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,094 control chromosomes in the GnomAD database, including 25,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (25001 hom., cov: 33)
• Consequence: ZNF365 NM_014951.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.203

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=-0.93).
• BP6: Variant 10-62377116-C-T is Benign according to our data. Variant chr10-62377116-C-T is described in ClinVar as [Benign]. Clinvar id is 1274224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_014951.3	c.743+180C>T		intron_variant		ENST00000395254.8
ZNF365	NM_199450.3	c.743+180C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395254.8	c.743+180C>T		intron_variant		1	NM_014951.3	P1
ZNF365	ENST00000395255.7	c.743+180C>T		intron_variant		1
ZNF365	ENST00000466727.1	n.106+2658C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83544 AN: 151976 Hom.: 24999 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.549 AC: 83566 AN: 152094 Hom.: 25001 Cov.: 33 AF XY: 0.554 AC XY: 41212 AN XY: 74342

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.558

Alfa AF: 0.619 Hom.: 27897

Bravo AF: 0.526

Asia WGS AF: 0.649 AC: 2252 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	-0.93
Cadd	Benign	2.0
Dann	Benign	0.55

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: rs1873687; hg19: chr10-64136875;