8-80487046-C-T

Variant names:

• chr8-80487046-C-T
• rs749169552
• NM_001105539.3:c.236C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001105539.3(ZBTB10):​c.236C>T​(p.Ala79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,518,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.809
• Publications: 0 publications found

Genes affected

ZBTB10 (HGNC:30953): (zinc finger and BTB domain containing 10) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.119217604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105539.3. 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
	ZBTB10	NM_001105539.3	MANE Select	c.236C>T	p.Ala79Val	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
	ZBTB10	NM_023929.5		c.236C>T	p.Ala79Val	missense	Exon 1 of 7	NP_076418.3
	ZBTB10	NM_001277145.2		c.96+1167C>T		intron	N/A	NP_001264074.1	Q96DT7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB10	ENST00000455036.8	TSL:2 MANE Select	c.236C>T	p.Ala79Val	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
	ZBTB10	ENST00000430430.5	TSL:5	c.236C>T	p.Ala79Val	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
	ZBTB10	ENST00000961791.1		c.236C>T	p.Ala79Val	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152062 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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000913 AC: 1 AN: 109564 AF XY: 0.0000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000112 AC: 153 AN: 1366432 Hom.: 0 Cov.: 34 AF XY: 0.000119 AC XY: 80 AN XY: 674332

African (AFR) AF: 0.00 AC: 0 AN: 28226

American (AMR) AF: 0.00 AC: 0 AN: 33404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24268

East Asian (EAS) AF: 0.00 AC: 0 AN: 33012

South Asian (SAS) AF: 0.00 AC: 0 AN: 77646

European-Finnish (FIN) AF: 0.0000281 AC: 1 AN: 35540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5386

European-Non Finnish (NFE) AF: 0.000136 AC: 146 AN: 1071922

Other (OTH) AF: 0.000105 AC: 6 AN: 57028

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74266

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

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000587 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.81
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.044
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.17	T
Polyphen		0.59	P
Vest4		0.074
MutPred		0.20		Gain of sheet (P = 0.0043)
MVP		0.043
MPC		1.6
ClinPred		0.44	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.087
Mutation Taster		=94/6	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: rs749169552; hg19: chr8-81399281;