rs2278415

Positions:

• chr19-51964950-T-A
• chr19-51964950-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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)

ACMG classification

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	UniProt
ZNF350	NM_021632.4	c.1503A>T	p.Arg501Ser	missense_variant	5/5	ENST00000243644.9
ZNF350-AS1	NR_103847.1	n.103-11441T>A		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21648 AN: 152078 Hom.: 1634 Cov.: 32

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

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.: 33 AF XY: 0.143 AC XY: 104229 AN XY: 727238

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.: 32 AF XY: 0.147 AC XY: 10949 AN XY: 74408

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	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.023
Sift	Benign	0.091	T
Sift4G	Benign	0.13	T
Polyphen		0.064	B
Vest4		0.036
MutPred		0.69		Gain of glycosylation at R501 (P = 0.0201);
MPC		0.24
ClinPred		0.014	T
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

Other links and lift over

dbSNP: rs2278415; hg19: chr19-52468203; COSMIC: COSV54708930; COSMIC: COSV54708930;