chr10-47368767-C-T

Variant names:

• chr10-47368767-C-T
• rs11204210
• NM_153034.4:c.63G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153034.4(ZNF488):​c.63G>A​(p.Gly21Gly) 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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF488	NM_153034.4	MANE Select	c.63G>A	p.Gly21Gly	synonymous	Exon 2 of 2	NP_694579.1
	ZNF488	NM_001346932.2		c.63G>A	p.Gly21Gly	synonymous	Exon 4 of 4	NP_001333861.1
	ZNF488	NM_001346933.2		c.63G>A	p.Gly21Gly	synonymous	Exon 3 of 3	NP_001333862.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF488	ENST00000585316.3	TSL:1 MANE Select	c.63G>A	p.Gly21Gly	synonymous	Exon 2 of 2	ENSP00000462269.1
	ZNF488	ENST00000591025.1	TSL:1	c.-153G>A		5_prime_UTR	Exon 2 of 3	ENSP00000468133.1

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

GnomAD2 exomes AF: 0.344 AC: 85496 AN: 248178 AF XY: 0.352

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 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

African (AFR) AF: 0.344 AC: 11501 AN: 33454

American (AMR) AF: 0.273 AC: 12172 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 9408 AN: 26052

East Asian (EAS) AF: 0.481 AC: 19090 AN: 39694

South Asian (SAS) AF: 0.437 AC: 37603 AN: 86046

European-Finnish (FIN) AF: 0.304 AC: 15959 AN: 52474

Middle Eastern (MID) AF: 0.407 AC: 2340 AN: 5754

European-Non Finnish (NFE) AF: 0.323 AC: 358658 AN: 1111436

Other (OTH) AF: 0.352 AC: 21218 AN: 60328

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

African (AFR) AF: 0.344 AC: 14293 AN: 41514

American (AMR) AF: 0.289 AC: 4420 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2546 AN: 5166

South Asian (SAS) AF: 0.438 AC: 2111 AN: 4824

European-Finnish (FIN) AF: 0.297 AC: 3143 AN: 10598

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22166 AN: 67980

Other (OTH) AF: 0.339 AC: 717 AN: 2114

Alfa AF: 0.327 Hom.: 5569

Bravo AF: 0.332

Asia WGS AF: 0.462 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.48
PhyloP100		-0.35

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

Other links and lift over

dbSNP: rs11204210; hg19: chr10-48370595;