16-57997216-C-T

Variant summary

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

The NM_020807.3(ZNF319):​c.1050G>A​(p.Met350Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

ZNF319
NM_020807.3 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF319NM_020807.3 linkc.1050G>A p.Met350Ile missense_variant Exon 2 of 2 ENST00000299237.3 NP_065858.1 Q9P2F9
ZNF319NM_001384365.1 linkc.1050G>A p.Met350Ile missense_variant Exon 2 of 2 NP_001371294.1
ZNF319NM_001384366.1 linkc.1050G>A p.Met350Ile missense_variant Exon 3 of 3 NP_001371295.1
ZNF319NM_001384367.1 linkc.1050G>A p.Met350Ile 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.1050G>A p.Met350Ile missense_variant Exon 2 of 2 1 NM_020807.3 ENSP00000299237.2 Q9P2F9

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 01, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1050G>A (p.M350I) 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 1050, causing the methionine (M) at amino acid position 350 to be replaced by an isoleucine (I). 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
0.65
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.75
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.043
D
Polyphen
0.99
D
Vest4
0.61
MutPred
0.55
Loss of MoRF binding (P = 0.0802);
MVP
0.18
MPC
2.2
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.52
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr16-58031120; API