chr6-26637643-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024639.5(ZNF322):​c.911G>A​(p.Cys304Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 14)
Exomes 𝑓: 8.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNF322
NM_024639.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0150
Variant links:
Genes affected
ZNF322 (HGNC:23640): (zinc finger protein 322) ZNF322A is a member of the zinc-finger transcription factor family and may regulate transcriptional activation in MAPK (see MAPK1; MIM 176948) signaling pathways (Li et al., 2004 [PubMed 15555580]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06061867).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF322NM_024639.5 linkc.911G>A p.Cys304Tyr missense_variant Exon 4 of 4 ENST00000415922.7 NP_078915.2 Q6U7Q0A0A024QZZ4
ZNF322NM_001242797.2 linkc.911G>A p.Cys304Tyr missense_variant Exon 5 of 5 NP_001229726.1 Q6U7Q0A0A024QZZ4
ZNF322NM_001242798.2 linkc.911G>A p.Cys304Tyr missense_variant Exon 3 of 3 NP_001229727.1 Q6U7Q0A0A024QZZ4
ZNF322NM_001242799.2 linkc.911G>A p.Cys304Tyr missense_variant Exon 3 of 3 NP_001229728.1 Q6U7Q0A0A024QZZ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF322ENST00000415922.7 linkc.911G>A p.Cys304Tyr missense_variant Exon 4 of 4 1 NM_024639.5 ENSP00000418897.1 Q6U7Q0

Frequencies

GnomAD3 genomes
Cov.:
14
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
8.79e-7
AC:
1
AN:
1137210
Hom.:
0
Cov.:
16
AF XY:
0.00
AC XY:
0
AN XY:
574392
show subpopulations
Gnomad4 AFR exome
AF:
0.0000333
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
14

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.911G>A (p.C304Y) alteration is located in exon 5 (coding exon 1) of the ZNF322 gene. This alteration results from a G to A substitution at nucleotide position 911, causing the cysteine (C) at amino acid position 304 to be replaced by a tyrosine (Y). 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
0.24
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
16
DANN
Benign
0.85
DEOGEN2
Benign
0.00075
T;T;T;T;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.61
.;.;.;T;.
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.061
T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.090
N;N;N;N;N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
0.95
N;.;.;.;N
REVEL
Benign
0.15
Sift
Benign
1.0
T;.;.;.;T
Sift4G
Benign
0.55
T;T;T;T;T
Polyphen
0.14
B;B;B;B;B
Vest4
0.24
MutPred
0.27
Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);Loss of stability (P = 0.0672);
MVP
0.21
ClinPred
0.45
T
GERP RS
4.6
Varity_R
0.15
gMVP
0.040

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: rs1388989086; hg19: chr6-26637871; API