chr19-51964883-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021632.4(ZNF350):​c.1570G>A​(p.Val524Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000786 in 1,612,358 control chromosomes in the GnomAD database, including 5 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 Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 3 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.72
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0044547915).
BP6
Variant 19-51964883-C-T is Benign according to our data. Variant chr19-51964883-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650380.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF350NM_021632.4 linkuse as main transcriptc.1570G>A p.Val524Ile missense_variant 5/5 ENST00000243644.9 NP_067645.3
ZNF350-AS1NR_103847.1 linkuse as main transcriptn.103-11508C>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.1570G>A p.Val524Ile missense_variant 5/51 NM_021632.4 ENSP00000243644 P1
ZNF350-AS1ENST00000595010.4 linkuse as main transcriptn.121-11508C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00114
AC:
173
AN:
152200
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.0844
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00119
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000675
AC:
169
AN:
250436
Hom.:
1
AF XY:
0.000724
AC XY:
98
AN XY:
135310
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000638
Gnomad ASJ exome
AF:
0.00140
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.00111
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000750
AC:
1095
AN:
1460040
Hom.:
3
Cov.:
31
AF XY:
0.000726
AC XY:
527
AN XY:
725934
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000717
Gnomad4 ASJ exome
AF:
0.00188
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.000860
Gnomad4 OTH exome
AF:
0.000564
GnomAD4 genome
AF:
0.00114
AC:
173
AN:
152318
Hom.:
2
Cov.:
33
AF XY:
0.00107
AC XY:
80
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00119
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00104
Hom.:
0
Bravo
AF:
0.00126
TwinsUK
AF:
0.00135
AC:
5
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00116
AC:
10
ExAC
AF:
0.000642
AC:
78
EpiCase
AF:
0.000491
EpiControl
AF:
0.00136

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022ZNF350: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
7.1
DANN
Benign
0.28
DEOGEN2
Benign
0.027
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0091
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.0045
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.72
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.20
N
REVEL
Benign
0.035
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.053
B
Vest4
0.054
MVP
0.22
MPC
0.17
ClinPred
0.014
T
GERP RS
-1.8
Varity_R
0.051
gMVP
0.075

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: rs4988337; hg19: chr19-52468136; COSMIC: COSV54709892; COSMIC: COSV54709892; API