chr20-63962894-G-A

Variant names:

• chr20-63962894-G-A
• rs2275294
• NM_020713.3:c.1969-113C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020713.3(ZNF512B):​c.1969-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,295,078 control chromosomes in the GnomAD database, including 48,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5614 hom., cov: 34)
  • Exomes 𝑓: 0.26 (43352 hom.)
• Consequence: ZNF512B NM_020713.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200
• Publications: 16 publications found

Genes affected

ZNF512B (HGNC:29212): (zinc finger protein 512B) Predicted to enable DNA binding activity and metal ion binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-63962894-G-A is Benign according to our data. Variant chr20-63962894-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020713.3. 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
	ZNF512B	NM_020713.3	MANE Select	c.1969-113C>T		intron	N/A	NP_065764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF512B	ENST00000369888.6	TSL:1 MANE Select	c.1969-113C>T		intron	N/A	ENSP00000358904.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38538 AN: 152032 Hom.: 5609 Cov.: 34

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.265 AC: 302780 AN: 1142928 Hom.: 43352 AF XY: 0.266 AC XY: 148791 AN XY: 559624

African (AFR) AF: 0.139 AC: 3597 AN: 25830

American (AMR) AF: 0.445 AC: 9749 AN: 21932

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 7214 AN: 18342

East Asian (EAS) AF: 0.533 AC: 18251 AN: 34218

South Asian (SAS) AF: 0.304 AC: 18807 AN: 61842

European-Finnish (FIN) AF: 0.265 AC: 8179 AN: 30854

Middle Eastern (MID) AF: 0.261 AC: 960 AN: 3678

European-Non Finnish (NFE) AF: 0.248 AC: 222646 AN: 897516

Other (OTH) AF: 0.275 AC: 13377 AN: 48716

GnomAD4 genome AF: 0.253 AC: 38557 AN: 152150 Hom.: 5614 Cov.: 34 AF XY: 0.257 AC XY: 19117 AN XY: 74372

African (AFR) AF: 0.147 AC: 6127 AN: 41540

American (AMR) AF: 0.383 AC: 5858 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2627 AN: 5144

South Asian (SAS) AF: 0.326 AC: 1577 AN: 4832

European-Finnish (FIN) AF: 0.255 AC: 2695 AN: 10588

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17503 AN: 67970

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.256 Hom.: 1579

Bravo AF: 0.259

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21665992)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.90
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs2275294; hg19: chr20-62594247; COSMIC: COSV53872143;