9-96417738-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153695.4(ZNF367):​c.295G>A​(p.Ala99Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,228,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZNF367
NM_153695.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
ZNF367 (HGNC:18320): (zinc finger protein 367) Enables DNA-binding transcription factor activity. Acts upstream of or within regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.13526443).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF367NM_153695.4 linkc.295G>A p.Ala99Thr missense_variant Exon 1 of 5 ENST00000375256.5 NP_710162.1 Q7RTV3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF367ENST00000375256.5 linkc.295G>A p.Ala99Thr missense_variant Exon 1 of 5 1 NM_153695.4 ENSP00000364405.4 Q7RTV3-1

Frequencies

GnomAD3 genomes
AF:
0.0000199
AC:
3
AN:
150954
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000987
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000296
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000121
AC:
13
AN:
1077536
Hom.:
0
Cov.:
30
AF XY:
0.0000137
AC XY:
7
AN XY:
509264
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:
0.000133
Gnomad4 NFE exome
AF:
0.0000109
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000199
AC:
3
AN:
150954
Hom.:
0
Cov.:
33
AF XY:
0.0000271
AC XY:
2
AN XY:
73686
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000987
Gnomad4 NFE
AF:
0.0000296
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.295G>A (p.A99T) alteration is located in exon 1 (coding exon 1) of the ZNF367 gene. This alteration results from a G to A substitution at nucleotide position 295, causing the alanine (A) at amino acid position 99 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
Benign
0.18
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.46
T
M_CAP
Pathogenic
0.40
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.16
N
REVEL
Benign
0.030
Sift
Benign
0.38
T
Sift4G
Benign
0.66
T
Polyphen
0.0010
B
Vest4
0.11
MutPred
0.41
Gain of glycosylation at A99 (P = 0.002);
MVP
0.068
MPC
1.1
ClinPred
0.10
T
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.045
gMVP
0.26

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: rs1398588680; hg19: chr9-99180020; API