NM_014951.3:c.245C>A

Variant names:

• chr10-62376438-C-A
• rs756669590
• NM_014951.3:c.245C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014951.3(ZNF365):​c.245C>A​(p.Pro82Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P82L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF365 NM_014951.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781
• Publications: 0 publications found

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]

ENSG00000285837 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03309989).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF365	NM_014951.3	MANE Select	c.245C>A	p.Pro82Gln	missense	Exon 2 of 5	NP_055766.2	Q70YC5-1
	ZNF365	NM_199450.3		c.245C>A	p.Pro82Gln	missense	Exon 2 of 5	NP_955522.1	Q70YC5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF365	ENST00000395254.8	TSL:1 MANE Select	c.245C>A	p.Pro82Gln	missense	Exon 2 of 5	ENSP00000378674.3	Q70YC5-1
	ENSG00000285837	ENST00000647733.1		c.245C>A	p.Pro82Gln	missense	Exon 2 of 8	ENSP00000502188.1
	ZNF365	ENST00000395255.7	TSL:1	c.245C>A	p.Pro82Gln	missense	Exon 2 of 5	ENSP00000378675.3	Q70YC5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.68
DANN	Benign	0.12
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.77	N
PhyloP100		0.78
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.038
Sift	Benign	0.98	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.22		Gain of helix (P = 0.0078)
MVP		0.061
MPC		0.21
ClinPred		0.038	T
GERP RS		1.6
Varity_R		0.031
gMVP		0.059
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs756669590; hg19: chr10-64136197; COSMIC: COSV67926242; COSMIC: COSV67926242;