chr10-62388476-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014951.3(ZNF365):ā€‹c.824T>Cā€‹(p.Ile275Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000892 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 33)
Exomes š‘“: 0.000093 ( 0 hom. )

Consequence

ZNF365
NM_014951.3 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF365NM_014951.3 linkuse as main transcriptc.824T>C p.Ile275Thr missense_variant 3/5 ENST00000395254.8
ZNF365NM_199450.3 linkuse as main transcriptc.824T>C p.Ile275Thr missense_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF365ENST00000395254.8 linkuse as main transcriptc.824T>C p.Ile275Thr missense_variant 3/51 NM_014951.3 P1Q70YC5-1
ZNF365ENST00000395255.7 linkuse as main transcriptc.824T>C p.Ile275Thr missense_variant 3/51 Q70YC5-2
ZNF365ENST00000466727.1 linkuse as main transcriptn.187T>C non_coding_transcript_exon_variant 2/41

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251438
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000930
AC:
136
AN:
1461886
Hom.:
0
Cov.:
51
AF XY:
0.0000935
AC XY:
68
AN XY:
727244
show subpopulations
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:
0.000121
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152226
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000567
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 21, 2023The c.824T>C (p.I275T) alteration is located in exon 3 (coding exon 2) of the ZNF365 gene. This alteration results from a T to C substitution at nucleotide position 824, causing the isoleucine (I) at amino acid position 275 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;.;.
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.82
D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.8
L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-4.2
D;D;D
REVEL
Uncertain
0.45
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.91
P;D;D
Vest4
0.98
MutPred
0.46
Gain of disorder (P = 0.015);Gain of disorder (P = 0.015);Gain of disorder (P = 0.015);
MVP
0.65
MPC
0.90
ClinPred
0.88
D
GERP RS
5.7
Varity_R
0.52
gMVP
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745708419; hg19: chr10-64148235; API