rs375914046

Variant names:

• chr10-62376533-C-A
• rs375914046
• NM_014951.3:c.340C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-62376533-C-A
• chr10-62376533-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014951.3(ZNF365):​c.340C>A​(p.Pro114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: ZNF365 NM_014951.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16599762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF365	NM_014951.3	c.340C>A	p.Pro114Thr	missense_variant	Exon 2 of 5	ENST00000395254.8	NP_055766.2
ZNF365	NM_199450.3	c.340C>A	p.Pro114Thr	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.340C>A	p.Pro114Thr	missense_variant	Exon 2 of 5	1	NM_014951.3	ENSP00000378674.3
ENSG00000285837	ENST00000647733.1	c.340C>A	p.Pro114Thr	missense_variant	Exon 2 of 8			ENSP00000502188.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.21	T;T;T
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.78	P;P;P
Vest4		0.32
MutPred		0.28		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.61
MPC		0.81
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs375914046; hg19: chr10-64136292;