rs11204210

chr10-47368767-C-T

Variant summary

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

The NM_153034.4(ZNF488):c.63G>A(p.Gly21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,611,982 control chromosomes in the GnomAD database, including 91,649 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 0.33 (8680 hom., cov: 33)
  • Exomes 𝑓: 0.33 (82969 hom.)
• Consequence: ZNF488 NM_153034.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

Genes affected

ZNF488 (HGNC:23535): (zinc finger protein 488) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in oligodendrocyte development; positive regulation of myelination; and regulation of transcription, DNA-templated. Predicted to act upstream of or within negative regulation of transcription, DNA-templated and positive regulation of oligodendrocyte differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.349 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF488	NM_153034.4	c.63G>A	p.Gly21=	synonymous_variant	2/2	ENST00000585316.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF488	ENST00000585316.3	c.63G>A	p.Gly21=	synonymous_variant	2/2	1	NM_153034.4	A2
ZNF488	ENST00000591025.1	c.-153G>A		5_prime_UTR_variant	2/3	1		P4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50873 AN: 152040 Hom.: 8668 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.336

GnomAD3 exomes AF: 0.344 AC: 85496 AN: 248178 Hom.: 15381 AF XY: 0.352 AC XY: 47373 AN XY: 134670

Gnomad AFR exome AF: 0.345

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.504

Gnomad SAS exome AF: 0.438

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.339

GnomAD4 exome AF: 0.334 AC: 487949 AN: 1459824 Hom.: 82969 Cov.: 47 AF XY: 0.338 AC XY: 245756 AN XY: 726196

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.335 AC: 50920 AN: 152158 Hom.: 8680 Cov.: 33 AF XY: 0.336 AC XY: 24993 AN XY: 74376

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.339

Alfa AF: 0.327 Hom.: 4908

Bravo AF: 0.332

Asia WGS AF: 0.462 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.0
Dann	Benign	0.48

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: rs11204210; hg19: chr10-48370595;