rs3130100

Variant names:

• chr6-33315989-T-C
• rs3130100
• NM_005453.5:c.928A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005453.5(ZBTB22):​c.928A>G​(p.Thr310Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,613,586 control chromosomes in the GnomAD database, including 230,792 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T310I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.54 (22195 hom., cov: 30)
  • Exomes 𝑓: 0.53 (208597 hom.)
• Consequence: ZBTB22 NM_005453.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62
• Publications: 55 publications found

Genes affected

ZBTB22 (HGNC:13085): (zinc finger and BTB domain containing 22) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3302328E-5).
• BP6: Variant 6-33315989-T-C is Benign according to our data. Variant chr6-33315989-T-C is described in ClinVar as Benign. ClinVar VariationId is 403519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005453.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB22	NM_005453.5	MANE Select	c.928A>G	p.Thr310Ala	missense	Exon 2 of 2	NP_005444.4
	ZBTB22	NM_001145338.2		c.928A>G	p.Thr310Ala	missense	Exon 2 of 2	NP_001138810.1	O15209

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB22	ENST00000431845.3	TSL:1 MANE Select	c.928A>G	p.Thr310Ala	missense	Exon 2 of 2	ENSP00000407545.2	O15209
	ZBTB22	ENST00000441117.2	TSL:1	c.928A>G	p.Thr310Ala	missense	Exon 2 of 2	ENSP00000413172.2
	ZBTB22	ENST00000898257.1		c.928A>G	p.Thr310Ala	missense	Exon 2 of 2	ENSP00000568316.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81662 AN: 151640 Hom.: 22160 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.532

GnomAD2 exomes AF: 0.540 AC: 135569 AN: 251230 AF XY: 0.547

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.553

GnomAD4 exome AF: 0.532 AC: 777628 AN: 1461828 Hom.: 208597 Cov.: 84 AF XY: 0.536 AC XY: 389921 AN XY: 727216

African (AFR) AF: 0.566 AC: 18937 AN: 33480

American (AMR) AF: 0.534 AC: 23886 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 14811 AN: 26134

East Asian (EAS) AF: 0.342 AC: 13578 AN: 39700

South Asian (SAS) AF: 0.643 AC: 55465 AN: 86258

European-Finnish (FIN) AF: 0.527 AC: 28126 AN: 53380

Middle Eastern (MID) AF: 0.542 AC: 3126 AN: 5768

European-Non Finnish (NFE) AF: 0.528 AC: 587174 AN: 1111994

Other (OTH) AF: 0.539 AC: 32525 AN: 60392

GnomAD4 genome AF: 0.539 AC: 81752 AN: 151758 Hom.: 22195 Cov.: 30 AF XY: 0.541 AC XY: 40124 AN XY: 74138

African (AFR) AF: 0.554 AC: 22935 AN: 41362

American (AMR) AF: 0.556 AC: 8489 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1984 AN: 3462

East Asian (EAS) AF: 0.370 AC: 1895 AN: 5124

South Asian (SAS) AF: 0.634 AC: 3048 AN: 4808

European-Finnish (FIN) AF: 0.527 AC: 5561 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.533 AC: 36189 AN: 67888

Other (OTH) AF: 0.531 AC: 1119 AN: 2108

Alfa AF: 0.535 Hom.: 94188

Bravo AF: 0.539

TwinsUK AF: 0.519 AC: 1923

ALSPAC AF: 0.522 AC: 2012

ESP6500AA AF: 0.558 AC: 2459

ESP6500EA AF: 0.541 AC: 4652

ExAC AF: 0.546 AC: 66275

Asia WGS AF: 0.500 AC: 1740 AN: 3478

EpiCase AF: 0.541

EpiControl AF: 0.536

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.58
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.000013	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.4	N
PhyloP100		1.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.051
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.56
ClinPred		0.0018	T
GERP RS		3.0
Varity_R		0.074
gMVP		0.044
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: rs3130100; hg19: chr6-33283766; COSMIC: COSV56467442; COSMIC: COSV56467442;