Variant rs2278415 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021632.4(ZNF350):c.1503A>T(p.Arg501Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,614,048 control chromosomes in the GnomAD database, including 17,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1637 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15406 hom. )

Consequence

ZNF350
NM_021632.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0670

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 links:

ZNF350-AS1 (HGNC:48598): (ZNF350 antisense RNA 1)

ZNF350-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038515925).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF350	NM_021632.4 linkuse as main transcript	c.1503A>T	p.Arg501Ser	missense_variant	5/5	ENST00000243644.9	NP_067645.3
ZNF350-AS1	NR_103847.1 linkuse as main transcript	n.103-11441T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF350	ENST00000243644.9 linkuse as main transcript	c.1503A>T	p.Arg501Ser	missense_variant	5/5	1	NM_021632.4	ENSP00000243644	P1
ZNF350-AS1	ENST00000595010.4 linkuse as main transcript	n.121-11441T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21648

AN:

152078

Hom.:

1634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.157

AC:

39435

AN:

251336

Hom.:

3414

AF XY:

0.159

AC XY:

21574

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.141

AC:

205803

AN:

1461852

Hom.:

15406

Cov.:

AF XY:

0.143

AC XY:

104229

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.142

AC:

21666

AN:

152196

Hom.:

1637

Cov.:

AF XY:

0.147

AC XY:

10949

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.109

Hom.:

340

Bravo

AF:

0.133

TwinsUK

AF:

0.128

AC:

473

ALSPAC

AF:

0.128

AC:

495

ESP6500AA

AF:

0.143

AC:

631

ESP6500EA

AF:

0.127

AC:

1096

ExAC

AF:

0.159

AC:

19255

Asia WGS

AF:

0.259

AC:

899

AN:

3478

EpiCase

AF:

0.126

EpiControl

AF:

0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.041

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.023

Sift

Benign

0.091

Sift4G

Benign

0.13

Polyphen

0.064

Vest4

0.036

MutPred

0.69

Gain of glycosylation at R501 (P = 0.0201);

MPC

0.24

ClinPred

0.014

GERP RS

2.0

Varity_R

0.24

gMVP

0.31

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over