NM_001369741.1:c.489T>C

Variant names:

• chr20-63790269-A-G
• rs755017
• NM_001369741.1:c.489T>C

Variant summary

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

The NM_001369741.1(ZBTB46):​c.489T>C​(p.Ala163Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,611,810 control chromosomes in the GnomAD database, including 21,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (3236 hom., cov: 33)
  • Exomes 𝑓: 0.14 (17790 hom.)
• Consequence: ZBTB46 NM_001369741.1 synonymous
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -2.03
• Publications: 83 publications found

Genes affected

ZBTB46 (HGNC:16094): (zinc finger and BTB domain containing 46) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of leukocyte differentiation. Predicted to be part of chromatin. 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=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369741.1. 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
	ZBTB46	NM_001369741.1	MANE Select	c.489T>C	p.Ala163Ala	synonymous	Exon 2 of 5	NP_001356670.1
	ZBTB46	NM_025224.4		c.489T>C	p.Ala163Ala	synonymous	Exon 2 of 5	NP_079500.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB46	ENST00000245663.9	TSL:5 MANE Select	c.489T>C	p.Ala163Ala	synonymous	Exon 2 of 5	ENSP00000245663.3
	ZBTB46	ENST00000302995.2	TSL:2	c.489T>C	p.Ala163Ala	synonymous	Exon 2 of 7	ENSP00000303102.2
	ZBTB46	ENST00000395104.5	TSL:2	c.489T>C	p.Ala163Ala	synonymous	Exon 1 of 4	ENSP00000378536.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27885 AN: 152104 Hom.: 3220 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.169 AC: 41719 AN: 247358 AF XY: 0.160

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.0654

Gnomad EAS exome AF: 0.461

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.143 AC: 209229 AN: 1459588 Hom.: 17790 Cov.: 32 AF XY: 0.142 AC XY: 103261 AN XY: 726044

African (AFR) AF: 0.284 AC: 9495 AN: 33456

American (AMR) AF: 0.193 AC: 8611 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 1655 AN: 26104

East Asian (EAS) AF: 0.440 AC: 17431 AN: 39640

South Asian (SAS) AF: 0.155 AC: 13335 AN: 86016

European-Finnish (FIN) AF: 0.123 AC: 6418 AN: 52390

Middle Eastern (MID) AF: 0.0895 AC: 516 AN: 5764

European-Non Finnish (NFE) AF: 0.128 AC: 142697 AN: 1111374

Other (OTH) AF: 0.150 AC: 9071 AN: 60336

GnomAD4 genome AF: 0.184 AC: 27948 AN: 152222 Hom.: 3236 Cov.: 33 AF XY: 0.183 AC XY: 13648 AN XY: 74418

African (AFR) AF: 0.285 AC: 11856 AN: 41546

American (AMR) AF: 0.180 AC: 2758 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2291 AN: 5144

South Asian (SAS) AF: 0.170 AC: 823 AN: 4832

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10608

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8247 AN: 68010

Other (OTH) AF: 0.147 AC: 310 AN: 2116

Alfa AF: 0.138 Hom.: 6495

Bravo AF: 0.191

Asia WGS AF: 0.324 AC: 1125 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Chronic osteomyelitis Other:1

Sep 01, 2016

Department of Orthopeadics and Traumatology, Nanfang Hospital

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.23
PhyloP100		-2.0
Mutation Taster		=98/2	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: rs755017; hg19: chr20-62421622; COSMIC: COSV55511069; COSMIC: COSV55511069;