rs10995170

chr10-62463624-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395255.7(ZNF365):c.981+3827T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,190 control chromosomes in the GnomAD database, including 6,849 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6849 hom., cov: 33)
• Consequence: ZNF365 ENST00000395255.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_199450.3	c.981+3827T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395255.7	c.981+3827T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45279 AN: 152070 Hom.: 6845 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.298 AC: 45326 AN: 152190 Hom.: 6849 Cov.: 33 AF XY: 0.301 AC XY: 22385 AN XY: 74416

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.282

Alfa AF: 0.296 Hom.: 7407

Bravo AF: 0.291

Asia WGS AF: 0.344 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	16
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10995170; hg19: chr10-64223383;