rs16985052

chr19-53577526-C-T

Variant summary

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

The NM_001079906.2(ZNF331):c.966C>T(p.Thr322=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,613,764 control chromosomes in the GnomAD database, including 5,027 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 0.10 (1213 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3814 hom.)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-4.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF331	NM_001079906.2	c.966C>T	p.Thr322=	synonymous_variant	6/6	ENST00000449416.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF331	ENST00000449416.6	c.966C>T	p.Thr322=	synonymous_variant	6/6	5	NM_001079906.2	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15735 AN: 151768 Hom.: 1214 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0181

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.0605 AC: 15223 AN: 251438 Hom.: 743 AF XY: 0.0568 AC XY: 7715 AN XY: 135908

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0675

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0168

Gnomad FIN exome AF: 0.0555

Gnomad NFE exome AF: 0.0659

Gnomad OTH exome AF: 0.0590

GnomAD4 exome AF: 0.0656 AC: 95949 AN: 1461878 Hom.: 3814 Cov.: 34 AF XY: 0.0634 AC XY: 46078 AN XY: 727238

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.0424

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0524

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.0700

GnomAD4 genome AF: 0.104 AC: 15753 AN: 151886 Hom.: 1213 Cov.: 33 AF XY: 0.102 AC XY: 7547 AN XY: 74214

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.0181

Gnomad4 FIN AF: 0.0535

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0801 Hom.: 470

Bravo AF: 0.110

Asia WGS AF: 0.0200 AC: 72 AN: 3478

EpiCase AF: 0.0686

EpiControl AF: 0.0717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.47
Dann	Benign	0.70

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: rs16985052; hg19: chr19-54080780;