chr6-151366201-T-C

Variant names:

• chr6-151366201-T-C
• rs200348339
• NM_020861.3:c.865A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_020861.3(ZBTB2):​c.865A>G​(p.Ser289Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ZBTB2 NM_020861.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0730
• Publications: 0 publications found

Genes affected

ZBTB2 (HGNC:20868): (zinc finger and BTB domain containing 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027762502).
• BP6: Variant 6-151366201-T-C is Benign according to our data. Variant chr6-151366201-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2403018.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020861.3. 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
	ZBTB2	NM_020861.3	MANE Select	c.865A>G	p.Ser289Gly	missense	Exon 3 of 3	NP_065912.1	Q8N680

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB2	ENST00000325144.5	TSL:1 MANE Select	c.865A>G	p.Ser289Gly	missense	Exon 3 of 3	ENSP00000323183.4	Q8N680
	ZBTB2	ENST00000869305.1		c.865A>G	p.Ser289Gly	missense	Exon 4 of 4	ENSP00000539364.1
	ZBTB2	ENST00000869306.1		c.865A>G	p.Ser289Gly	missense	Exon 4 of 4	ENSP00000539365.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251352 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 155 AN: 1461894 Hom.: 0 Cov.: 34 AF XY: 0.0000976 AC XY: 71 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1112012

Other (OTH) AF: 0.000132 AC: 8 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Likely 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	0.061
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.58
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.073
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.037
Sift	Benign	0.43	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.029
MVP		0.27
MPC		0.51
ClinPred		0.015	T
GERP RS		-2.1
Varity_R		0.020
gMVP		0.27
Mutation Taster		=95/5	polymorphism

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: rs200348339; hg19: chr6-151687336;