19-12045012-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001080404.3(ZNF878):​c.389T>G​(p.Leu130Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF878
NM_001080404.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11
Variant links:
Genes affected
ZNF878 (HGNC:37246): (zinc finger protein 878) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]
ZNF433-AS1 (HGNC:53776): (ZNF433 and ZNF878 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF878NM_001080404.3 linkuse as main transcriptc.389T>G p.Leu130Arg missense_variant 4/4 ENST00000547628.2 NP_001073873.2
ZNF433-AS1NR_134928.1 linkuse as main transcriptn.476-1070A>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF878ENST00000547628.2 linkuse as main transcriptc.389T>G p.Leu130Arg missense_variant 4/43 NM_001080404.3 ENSP00000447931 P1
ZNF433-AS1ENST00000476474.5 linkuse as main transcriptn.414-1070A>C intron_variant, non_coding_transcript_variant 2
ZNF433-AS1ENST00000591838.5 linkuse as main transcriptn.237-1070A>C intron_variant, non_coding_transcript_variant 5
ZNF433-AS1ENST00000591898.1 linkuse as main transcriptn.163-1070A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsJan 09, 2024The c.389T>G (p.L130R) alteration is located in exon 4 (coding exon 4) of the ZNF878 gene. This alteration results from a T to G substitution at nucleotide position 389, causing the leucine (L) at amino acid position 130 to be replaced by an arginine (R). 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
0.16
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.077
T
Eigen
Benign
-0.39
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.0012
T
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.99
T
MutationAssessor
Pathogenic
3.2
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.1
D
REVEL
Benign
0.090
Sift
Benign
0.097
T
Sift4G
Uncertain
0.0070
D
Polyphen
0.99
D
Vest4
0.46
MutPred
0.79
Gain of MoRF binding (P = 0.0137);
MVP
0.26
MPC
0.84
ClinPred
0.49
T
GERP RS
-2.4
Varity_R
0.22
gMVP
0.082

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: chr19-12155827; API