19-56664306-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005850.3(ZNF835):​c.893G>T​(p.Arg298Leu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Consequence

ZNF835
NM_001005850.3 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.158
Variant links:
Genes affected
ZNF835 (HGNC:34332): (zinc finger protein 835) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18394199).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF835NM_001005850.3 linkc.893G>T p.Arg298Leu missense_variant Exon 2 of 2 ENST00000537055.4 NP_001005850.2 Q9Y2P0
ZNF835XM_005259382.3 linkc.893G>T p.Arg298Leu missense_variant Exon 2 of 2 XP_005259439.1 Q9Y2P0
ZNF835XM_005259383.4 linkc.893G>T p.Arg298Leu missense_variant Exon 2 of 2 XP_005259440.1 Q9Y2P0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF835ENST00000537055.4 linkc.893G>T p.Arg298Leu missense_variant Exon 2 of 2 2 NM_001005850.3 ENSP00000444747.1 Q9Y2P0
ZIM2-AS1ENST00000650950.1 linkn.202-2971C>A intron_variant Intron 2 of 5

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Cov.:
80
GnomAD4 genome
Cov.:
35

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.893G>T (p.R298L) alteration is located in exon 2 (coding exon 1) of the ZNF835 gene. This alteration results from a G to T substitution at nucleotide position 893, causing the arginine (R) at amino acid position 298 to be replaced by a leucine (L). 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
Uncertain
0.55
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.063
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Benign
0.028
Sift
Uncertain
0.0030
D
Sift4G
Pathogenic
0.0010
D
Vest4
0.26
MVP
0.19
ClinPred
0.97
D
GERP RS
2.1
Varity_R
0.51
gMVP
0.053

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: chr19-57175674; API