chr10-62376438-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF365	NM_014951.3	c.245C>A	p.Pro82Gln	missense_variant	Exon 2 of 5	ENST00000395254.8	NP_055766.2
ZNF365	NM_199450.3	c.245C>A	p.Pro82Gln	missense_variant	Exon 2 of 5		NP_955522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF365	ENST00000395254.8	c.245C>A	p.Pro82Gln	missense_variant	Exon 2 of 5	1	NM_014951.3	ENSP00000378674.3
ENSG00000285837	ENST00000647733.1	c.245C>A	p.Pro82Gln	missense_variant	Exon 2 of 8			ENSP00000502188.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.77	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.98	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.12
MutPred		0.22		Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);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

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

No publications associated with this variant yet.

Other links and lift over

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