19-53576890-A-G

Position:

• chr19-53576890-A-G

Variant summary

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

The NM_001079906.2(ZNF331):​c.330A>G​(p.Arg110Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,613,858 control chromosomes in the GnomAD database, including 417,751 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 0.75 (43648 hom., cov: 31)
  • Exomes 𝑓: 0.71 (374103 hom.)
• Consequence: ZNF331 NM_001079906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.643 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.330A>G	p.Arg110Arg	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.330A>G	p.Arg110Arg	synonymous_variant	6/6	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114141 AN: 151914 Hom.: 43608 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.747

GnomAD3 exomes AF: 0.697 AC: 175239 AN: 251376 Hom.: 61838 AF XY: 0.700 AC XY: 95072 AN XY: 135868

Gnomad AFR exome AF: 0.897

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.671

Gnomad SAS exome AF: 0.697

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.720

Gnomad OTH exome AF: 0.709

GnomAD4 exome AF: 0.714 AC: 1043547 AN: 1461826 Hom.: 374103 Cov.: 58 AF XY: 0.714 AC XY: 518976 AN XY: 727216

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.751 AC: 114244 AN: 152032 Hom.: 43648 Cov.: 31 AF XY: 0.745 AC XY: 55335 AN XY: 74288

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.747

Alfa AF: 0.725 Hom.: 78519

Bravo AF: 0.756

Asia WGS AF: 0.704 AC: 2449 AN: 3478

EpiCase AF: 0.714

EpiControl AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.58

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: rs8109631; hg19: chr19-54080144; COSMIC: COSV53475694; COSMIC: COSV53475694;