rs1056393

Positions:

• chr19-53577745-A-G
• chr19-53577745-A-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.1185A>G​(p.Gly395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,614,054 control chromosomes in the GnomAD database, including 5,042 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 (1216 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3826 hom.)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23

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=-0.85).
• BP7: Synonymous conserved (PhyloP=-4.23 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	Protein	UniProt
ZNF331	NM_001079906.2	c.1185A>G	p.Gly395=	synonymous_variant	6/6	ENST00000449416.6	NP_001073375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6	c.1185A>G	p.Gly395=	synonymous_variant	6/6	5	NM_001079906.2	ENSP00000393817	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15760 AN: 152066 Hom.: 1217 Cov.: 33

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.0606 AC: 15235 AN: 251376 Hom.: 746 AF XY: 0.0568 AC XY: 7720 AN XY: 135880

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0383

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: 0.0660

Gnomad OTH exome AF: 0.0589

GnomAD4 exome AF: 0.0657 AC: 96009 AN: 1461870 Hom.: 3826 Cov.: 34 AF XY: 0.0634 AC XY: 46097 AN XY: 727244

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.0423

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0523

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.0700

GnomAD4 genome AF: 0.104 AC: 15778 AN: 152184 Hom.: 1216 Cov.: 33 AF XY: 0.102 AC XY: 7565 AN XY: 74416

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0660

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0738 Hom.: 882

Bravo AF: 0.110

Asia WGS AF: 0.0200 AC: 72 AN: 3478

EpiCase AF: 0.0687

EpiControl AF: 0.0717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.68
DANN	Benign	0.60

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: rs1056393; hg19: chr19-54080999;