19-56663959-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.1240G>A​(p.Gly414Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,613,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ZNF835
NM_001005850.3 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01
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]

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=0.010751605).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF835NM_001005850.3 linkuse as main transcriptc.1240G>A p.Gly414Arg missense_variant 2/2 ENST00000537055.4 NP_001005850.2 Q9Y2P0
ZNF835XM_005259382.3 linkuse as main transcriptc.1240G>A p.Gly414Arg missense_variant 2/2 XP_005259439.1 Q9Y2P0
ZNF835XM_005259383.4 linkuse as main transcriptc.1240G>A p.Gly414Arg missense_variant 2/2 XP_005259440.1 Q9Y2P0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF835ENST00000537055.4 linkuse as main transcriptc.1240G>A p.Gly414Arg missense_variant 2/22 NM_001005850.3 ENSP00000444747.1 Q9Y2P0
ZIM2-AS1ENST00000650950.1 linkuse as main transcriptn.202-3318C>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.000731
AC:
111
AN:
151950
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00261
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000149
AC:
37
AN:
248966
Hom.:
0
AF XY:
0.000126
AC XY:
17
AN XY:
135100
show subpopulations
Gnomad AFR exome
AF:
0.00218
Gnomad AMR exome
AF:
0.0000870
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1460984
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
726834
show subpopulations
Gnomad4 AFR exome
AF:
0.00128
Gnomad4 AMR exome
AF:
0.000112
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000730
AC:
111
AN:
152070
Hom.:
0
Cov.:
33
AF XY:
0.000659
AC XY:
49
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00260
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000279
Hom.:
0
Bravo
AF:
0.000790
ESP6500AA
AF:
0.00183
AC:
8
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000181
AC:
22
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 GeneticsDec 21, 2022The c.1240G>A (p.G414R) 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 1240, causing the glycine (G) at amino acid position 414 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
Pathogenic
0.75
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.066
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.011
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Benign
0.046
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0060
D
Vest4
0.12
MVP
0.27
ClinPred
0.36
T
GERP RS
1.1
Varity_R
0.56
gMVP
0.038

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: rs375406315; hg19: chr19-57175327; COSMIC: COSV73379295; COSMIC: COSV73379295; API