chr19-51965078-C-T

Variant summary

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

The NM_021632.4(ZNF350):​c.1375G>A​(p.Gly459Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.42
Variant links:
Genes affected
ZNF350 (HGNC:16656): (zinc finger protein 350) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]
ZNF350-AS1 (HGNC:48598): (ZNF350 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=0.01868996).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF350NM_021632.4 linkuse as main transcriptc.1375G>A p.Gly459Arg missense_variant 5/5 ENST00000243644.9 NP_067645.3
ZNF350-AS1NR_103847.1 linkuse as main transcriptn.103-11313C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF350ENST00000243644.9 linkuse as main transcriptc.1375G>A p.Gly459Arg missense_variant 5/51 NM_021632.4 ENSP00000243644 P1
ZNF350-AS1ENST00000595010.4 linkuse as main transcriptn.121-11313C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251316
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000491
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:
0.0000176
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.0000458
AC:
67
AN:
1461882
Hom.:
0
Cov.:
34
AF XY:
0.0000426
AC XY:
31
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.000151
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10

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.1375G>A (p.G459R) alteration is located in exon 5 (coding exon 4) of the ZNF350 gene. This alteration results from a G to A substitution at nucleotide position 1375, causing the glycine (G) at amino acid position 459 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
0.11
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
7.3
DANN
Benign
0.44
DEOGEN2
Benign
0.018
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.20
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.19
T
PROVEAN
Benign
0.60
N
REVEL
Benign
0.015
Sift
Benign
0.42
T
Sift4G
Benign
0.51
T
Polyphen
0.0020
B
Vest4
0.16
MutPred
0.35
Gain of MoRF binding (P = 0.0261);
MVP
0.15
MPC
0.24
ClinPred
0.013
T
GERP RS
-7.2
Varity_R
0.017
gMVP
0.092

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: rs142789660; hg19: chr19-52468331; API