7-99487121-A-C

Variant summary

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

The NM_213603.3(ZNF789):​c.911A>C​(p.Gln304Pro) variant causes a missense change involving the alteration of a non-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: 33)

Consequence

ZNF789
NM_213603.3 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.459
Variant links:
Genes affected
ZNF789 (HGNC:27801): (zinc finger protein 789) Predicted to enable DNA-binding transcription factor 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. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
ZNF394 (HGNC:18832): (zinc finger protein 394) The protein encoded by this gene is a zinc finger protein that inhibits the transcription of mitogen-activated protein kinase signaling pathways. The encoded protein may be involved in cardiac function. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

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/exons MANE Protein UniProt
ZNF789NM_213603.3 linkuse as main transcriptc.911A>C p.Gln304Pro missense_variant 5/5 ENST00000331410.10 NP_998768.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF789ENST00000331410.10 linkuse as main transcriptc.911A>C p.Gln304Pro missense_variant 5/51 NM_213603.3 ENSP00000331927 P1Q5FWF6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 11, 2021The c.911A>C (p.Q304P) alteration is located in exon 5 (coding exon 4) of the ZNF789 gene. This alteration results from a A to C substitution at nucleotide position 911, causing the glutamine (Q) at amino acid position 304 to be replaced by a proline (P). 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
0.98
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
24
DANN
Benign
0.95
DEOGEN2
Benign
0.083
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.12
N
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.0059
T
MetaRNN
Uncertain
0.44
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Benign
0.064
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.98
D
Vest4
0.42
MutPred
0.53
Gain of relative solvent accessibility (P = 0.0522);
MVP
0.29
MPC
0.80
ClinPred
0.48
T
GERP RS
1.5
Varity_R
0.63
gMVP
0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99084744; API