16-57997893-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020807.3(ZNF319):​c.373G>A​(p.Val125Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,613,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ZNF319
NM_020807.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
Variant links:
Genes affected
ZNF319 (HGNC:13644): (zinc finger protein 319) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.10220915).
BS2
High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF319NM_020807.3 linkc.373G>A p.Val125Met missense_variant Exon 2 of 2 ENST00000299237.3 NP_065858.1 Q9P2F9
ZNF319NM_001384365.1 linkc.373G>A p.Val125Met missense_variant Exon 2 of 2 NP_001371294.1
ZNF319NM_001384366.1 linkc.373G>A p.Val125Met missense_variant Exon 3 of 3 NP_001371295.1
ZNF319NM_001384367.1 linkc.373G>A p.Val125Met missense_variant Exon 3 of 3 NP_001371296.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF319ENST00000299237.3 linkc.373G>A p.Val125Met missense_variant Exon 2 of 2 1 NM_020807.3 ENSP00000299237.2 Q9P2F9
ZNF319ENST00000562909.1 linkc.*166G>A downstream_gene_variant 5 ENSP00000457048.1 H3BT69

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152268
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000797
AC:
20
AN:
250872
Hom.:
0
AF XY:
0.0000884
AC XY:
12
AN XY:
135766
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000753
AC:
110
AN:
1461166
Hom.:
0
Cov.:
33
AF XY:
0.0000688
AC XY:
50
AN XY:
726898
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000890
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152386
Hom.:
0
Cov.:
34
AF XY:
0.0000805
AC XY:
6
AN XY:
74520
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000201
Hom.:
0
Bravo
AF:
0.000121
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.00
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.373G>A (p.V125M) alteration is located in exon 2 (coding exon 1) of the ZNF319 gene. This alteration results from a G to A substitution at nucleotide position 373, causing the valine (V) at amino acid position 125 to be replaced by a methionine (M). 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
0.15
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
23
DANN
Benign
0.93
DEOGEN2
Benign
0.076
T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.62
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.11
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.074
T
Polyphen
0.97
D
Vest4
0.12
MVP
0.043
MPC
1.0
ClinPred
0.048
T
GERP RS
1.9
Varity_R
0.094
gMVP
0.19

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: rs145368309; hg19: chr16-58031797; API