rs2278420

Positions:

• chr19-51968619-A-G

Variant summary

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

The NM_021632.4(ZNF350):​c.197T>C​(p.Leu66Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,762 control chromosomes in the GnomAD database, including 29,013 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.24 (5017 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23996 hom.)
• Consequence: ZNF350 NM_021632.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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=0.0038086176).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF350	NM_021632.4	c.197T>C	p.Leu66Pro	missense_variant	4/5	ENST00000243644.9
ZNF350-AS1	NR_103847.1	n.103-7772A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF350	ENST00000243644.9	c.197T>C	p.Leu66Pro	missense_variant	4/5	1	NM_021632.4	P1
ZNF350-AS1	ENST00000595010.4	n.121-7772A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35738 AN: 151900 Hom.: 4989 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.203 AC: 51077 AN: 251432 Hom.: 5679 AF XY: 0.201 AC XY: 27304 AN XY: 135892

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.222

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.174 AC: 254920 AN: 1461742 Hom.: 23996 Cov.: 33 AF XY: 0.176 AC XY: 128082 AN XY: 727178

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.236 AC: 35828 AN: 152020 Hom.: 5017 Cov.: 32 AF XY: 0.240 AC XY: 17831 AN XY: 74318

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.220

Alfa AF: 0.174 Hom.: 5532

Bravo AF: 0.233

TwinsUK AF: 0.160 AC: 593

ALSPAC AF: 0.154 AC: 594

ESP6500AA AF: 0.375 AC: 1654

ESP6500EA AF: 0.156 AC: 1340

ExAC AF: 0.208 AC: 25232

Asia WGS AF: 0.308 AC: 1069 AN: 3478

EpiCase AF: 0.154

EpiControl AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.29
DANN	Benign	0.039
DEOGEN2	Benign	0.011	T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00060	N
LIST_S2	Benign	0.089	T;T;T
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.8	N;.;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	4.4	N;.;.
REVEL	Benign	0.025
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.073
MPC		0.31
ClinPred		0.00058	T
GERP RS		0.91
Varity_R		0.050
gMVP		0.021

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: rs2278420; hg19: chr19-52471872; COSMIC: COSV54708966; COSMIC: COSV54708966;