rs10995170

Variant names:

• chr10-62463624-T-C
• rs10995170
• ENST00000647733.1:c.981+3827T>C

Variant summary

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

The ENST00000647733.1(ENSG00000285837):​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: ENSG00000285837 ENST00000647733.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• Publications: 7 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=-0.54).
• 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 rank	MANE	Protein	UniProt
ZNF365	NM_199450.3	c.981+3827T>C		intron_variant	Intron 4 of 4		NP_955522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285837	ENST00000647733.1	c.981+3827T>C		intron_variant	Intron 4 of 7			ENSP00000502188.1
ZNF365	ENST00000395255.7	c.981+3827T>C		intron_variant	Intron 4 of 4	1		ENSP00000378675.3

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

African (AFR) AF: 0.267 AC: 11084 AN: 41500

American (AMR) AF: 0.311 AC: 4760 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1690 AN: 5182

South Asian (SAS) AF: 0.351 AC: 1695 AN: 4826

European-Finnish (FIN) AF: 0.362 AC: 3830 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20227 AN: 68008

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.297 Hom.: 19746

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
PhyloP100		0.50
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: rs10995170; hg19: chr10-64223383;