chr19-51965131-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.1322G>A​(p.Arg441Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 1,614,094 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00038 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.585
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=0.023962408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF350NM_021632.4 linkuse as main transcriptc.1322G>A p.Arg441Lys missense_variant 5/5 ENST00000243644.9 NP_067645.3
ZNF350-AS1NR_103847.1 linkuse as main transcriptn.103-11260C>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.1322G>A p.Arg441Lys missense_variant 5/51 NM_021632.4 ENSP00000243644 P1
ZNF350-AS1ENST00000595010.4 linkuse as main transcriptn.121-11260C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.000381
AC:
58
AN:
152200
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000750
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000247
AC:
62
AN:
251400
Hom.:
0
AF XY:
0.000265
AC XY:
36
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000440
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000549
AC:
802
AN:
1461894
Hom.:
0
Cov.:
34
AF XY:
0.000520
AC XY:
378
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000674
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000381
AC:
58
AN:
152200
Hom.:
1
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000750
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000492
Hom.:
0
Bravo
AF:
0.000351
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000814
AC:
7
ExAC
AF:
0.000206
AC:
25
EpiCase
AF:
0.000491
EpiControl
AF:
0.000415

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 16, 2022The c.1322G>A (p.R441K) 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 1322, causing the arginine (R) at amino acid position 441 to be replaced by a lysine (K). 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
0.083
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
4.9
DANN
Benign
0.40
DEOGEN2
Benign
0.012
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.0081
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
0.33
N
REVEL
Benign
0.036
Sift
Benign
0.54
T
Sift4G
Benign
0.93
T
Polyphen
0.017
B
Vest4
0.044
MVP
0.14
MPC
0.20
ClinPred
0.022
T
GERP RS
-6.1
Varity_R
0.035
gMVP
0.058

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: rs144263666; hg19: chr19-52468384; API