10-62427805-C-T

Variant names:

• chr10-62427805-C-T
• rs7089814
• ENST00000647733.1:c.925-31936C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647733.1(ENSG00000285837):​c.925-31936C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,930 control chromosomes in the GnomAD database, including 22,976 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 0.54 (22976 hom., cov: 31)
• Consequence: ENSG00000285837 ENST00000647733.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 21 publications found

Genes affected

ENSG00000285837 (HGNC:):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF365	NM_199450.3	c.925-31936C>T		intron_variant	Intron 3 of 4		NP_955522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285837	ENST00000647733.1	c.925-31936C>T		intron_variant	Intron 3 of 7			ENSP00000502188.1
ZNF365	ENST00000395255.7	c.925-31936C>T		intron_variant	Intron 3 of 4	1		ENSP00000378675.3

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81259 AN: 151812 Hom.: 22965 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.535 AC: 81293 AN: 151930 Hom.: 22976 Cov.: 31 AF XY: 0.533 AC XY: 39547 AN XY: 74236

African (AFR) AF: 0.352 AC: 14578 AN: 41426

American (AMR) AF: 0.561 AC: 8569 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1955 AN: 3470

East Asian (EAS) AF: 0.684 AC: 3523 AN: 5154

South Asian (SAS) AF: 0.481 AC: 2310 AN: 4802

European-Finnish (FIN) AF: 0.596 AC: 6278 AN: 10528

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42207 AN: 67966

Other (OTH) AF: 0.542 AC: 1142 AN: 2108

Alfa AF: 0.589 Hom.: 76026

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.33
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7089814; hg19: chr10-64187564;