16-68564104-A-G

Position:

• chr16-68564104-A-G

Variant summary

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

The NM_001305203.2(ZFP90):​c.1317A>G​(p.Gln439=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,613,866 control chromosomes in the GnomAD database, including 292,441 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 0.51 (22087 hom., cov: 32)
  • Exomes 𝑓: 0.60 (270354 hom.)
• Consequence: ZFP90 NM_001305203.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

Genes affected

ZFP90 (HGNC:23329): (ZFP90 zinc finger protein) This gene encodes a member of the zinc finger protein family that modulates gene expression. The encoded protein derepresses the transcription of certain fetal cardiac genes and may contribute to the genetic reprogramming that occurs during the development of heart failure. Genome wide association studies have identified this gene among ulcerative colitis risk loci. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.029 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP90	NM_001305203.2	c.1317A>G	p.Gln439=	synonymous_variant	5/5	ENST00000563169.7	NP_001292132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP90	ENST00000563169.7	c.1317A>G	p.Gln439=	synonymous_variant	5/5	1	NM_001305203.2	ENSP00000454418	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78083 AN: 151924 Hom.: 22077 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.528

GnomAD3 exomes AF: 0.603 AC: 150515 AN: 249410 Hom.: 46788 AF XY: 0.610 AC XY: 82505 AN XY: 135322

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.577

Gnomad EAS exome AF: 0.757

Gnomad SAS exome AF: 0.672

Gnomad FIN exome AF: 0.631

Gnomad NFE exome AF: 0.605

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.604 AC: 883640 AN: 1461824 Hom.: 270354 Cov.: 74 AF XY: 0.607 AC XY: 441479 AN XY: 727216

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.671

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.514 AC: 78102 AN: 152042 Hom.: 22087 Cov.: 32 AF XY: 0.520 AC XY: 38659 AN XY: 74352

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.529

Alfa AF: 0.575 Hom.: 32065

Bravo AF: 0.497

Asia WGS AF: 0.601 AC: 2090 AN: 3478

EpiCase AF: 0.590

EpiControl AF: 0.590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.9
DANN	Benign	0.71

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: rs1177648; hg19: chr16-68598007;