19-51965074-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021632.4(ZNF350):​c.1379C>T​(p.Ala460Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 1,614,114 control chromosomes in the GnomAD database, including 7 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 4 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.979
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 -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005579084).
BP6
Variant 19-51965074-G-A is Benign according to our data. Variant chr19-51965074-G-A is described in ClinVar as [Benign]. Clinvar id is 712253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF350NM_021632.4 linkuse as main transcriptc.1379C>T p.Ala460Val missense_variant 5/5 ENST00000243644.9
ZNF350-AS1NR_103847.1 linkuse as main transcriptn.103-11317G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF350ENST00000243644.9 linkuse as main transcriptc.1379C>T p.Ala460Val missense_variant 5/51 NM_021632.4 P1
ZNF350-AS1ENST00000595010.4 linkuse as main transcriptn.121-11317G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00356
AC:
541
AN:
152136
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0122
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.00107
AC:
269
AN:
251280
Hom.:
1
AF XY:
0.000832
AC XY:
113
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.0127
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000413
AC:
604
AN:
1461860
Hom.:
4
Cov.:
34
AF XY:
0.000389
AC XY:
283
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0123
Gnomad4 AMR exome
AF:
0.00116
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000692
Gnomad4 OTH exome
AF:
0.000944
GnomAD4 genome
AF:
0.00355
AC:
541
AN:
152254
Hom.:
3
Cov.:
32
AF XY:
0.00356
AC XY:
265
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0121
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.000784
Hom.:
0
Bravo
AF:
0.00400
ESP6500AA
AF:
0.0143
AC:
63
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00123
AC:
149
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
3.1
DANN
Benign
0.069
DEOGEN2
Benign
0.017
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0034
N
LIST_S2
Benign
0.19
T
MetaRNN
Benign
0.0056
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-2.5
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
2.6
N
REVEL
Benign
0.057
Sift
Benign
1.0
T
Sift4G
Benign
0.67
T
Polyphen
0.0
B
Vest4
0.11
MVP
0.16
MPC
0.19
ClinPred
0.0066
T
GERP RS
3.8
Varity_R
0.020
gMVP
0.044

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: rs115151289; hg19: chr19-52468327; COSMIC: COSV99702681; COSMIC: COSV99702681; API