19-56663703-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005850.3(ZNF835):​c.1496G>A​(p.Ser499Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF835
NM_001005850.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06255272).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF835NM_001005850.3 linkc.1496G>A p.Ser499Asn missense_variant Exon 2 of 2 ENST00000537055.4 NP_001005850.2 Q9Y2P0
ZNF835XM_005259382.3 linkc.1496G>A p.Ser499Asn missense_variant Exon 2 of 2 XP_005259439.1 Q9Y2P0
ZNF835XM_005259383.4 linkc.1496G>A p.Ser499Asn 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.1496G>A p.Ser499Asn missense_variant Exon 2 of 2 2 NM_001005850.3 ENSP00000444747.1 Q9Y2P0
ZIM2-AS1ENST00000650950.1 linkn.202-3574C>T intron_variant Intron 2 of 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461662
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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.:
33
Bravo
AF:
0.0000227

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1496G>A (p.S499N) alteration is located in exon 2 (coding exon 1) of the ZNF835 gene. This alteration results from a G to A substitution at nucleotide position 1496, causing the serine (S) at amino acid position 499 to be replaced by an asparagine (N). 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
0.11
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
8.6
DANN
Benign
0.91
DEOGEN2
Benign
0.00076
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.098
T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.31
N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.17
N
REVEL
Benign
0.059
Sift
Benign
0.23
T
Sift4G
Uncertain
0.028
D
Vest4
0.092
MVP
0.076
ClinPred
0.096
T
GERP RS
-3.4
Varity_R
0.054
gMVP
0.010

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: rs917684351; hg19: chr19-57175071; API