chr19-51965745-A-G

Position:

• chr19-51965745-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021632.4(ZNF350):​c.708T>C​(p.Cys236Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,812 control chromosomes in the GnomAD database, including 21,441 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3278 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18163 hom.)
• Consequence: ZNF350 NM_021632.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF350	NM_021632.4	c.708T>C	p.Cys236Cys	synonymous_variant	5/5	ENST00000243644.9	NP_067645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF350	ENST00000243644.9	c.708T>C	p.Cys236Cys	synonymous_variant	5/5	1	NM_021632.4	ENSP00000243644.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29549 AN: 151868 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.175 AC: 43912 AN: 251304 Hom.: 4229 AF XY: 0.174 AC XY: 23572 AN XY: 135820

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.221

Gnomad SAS exome AF: 0.246

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.152 AC: 222041 AN: 1461826 Hom.: 18163 Cov.: 34 AF XY: 0.154 AC XY: 111844 AN XY: 727218

Gnomad4 AFR exome AF: 0.301

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.195 AC: 29606 AN: 151986 Hom.: 3278 Cov.: 32 AF XY: 0.198 AC XY: 14682 AN XY: 74312

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.177

Alfa AF: 0.141 Hom.: 2212

Bravo AF: 0.193

Asia WGS AF: 0.276 AC: 958 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.37

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: rs4988334; hg19: chr19-52468998; COSMIC: COSV54707662; COSMIC: COSV54707662;