8-80486950-C-T

Variant names:

• chr8-80486950-C-T
• rs573842562
• NM_001105539.3:c.140C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001105539.3(ZBTB10):​c.140C>T​(p.Pro47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,514,066 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (24 hom.)
• Consequence: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006051153).
• BS2: High Homozygotes in GnomAdExome4 at 24 gene

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.140C>T	p.Pro47Leu	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
	ZBTB10	NM_023929.5		c.140C>T	p.Pro47Leu	missense	Exon 1 of 7	NP_076418.3
	ZBTB10	NM_001277145.2		c.96+1071C>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.140C>T	p.Pro47Leu	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
	ZBTB10	ENST00000430430.5	TSL:5	c.140C>T	p.Pro47Leu	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
	ZBTB10	ENST00000961791.1		c.140C>T	p.Pro47Leu	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes AF: 0.00347 AC: 527 AN: 151690 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00261

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00930

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00515

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00324 AC: 339 AN: 104488 AF XY: 0.00303

Gnomad AFR exome AF: 0.000992

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00236

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.00528

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.00472 AC: 6425 AN: 1362268 Hom.: 24 Cov.: 34 AF XY: 0.00467 AC XY: 3138 AN XY: 671868

African (AFR) AF: 0.000647 AC: 18 AN: 27836

American (AMR) AF: 0.00167 AC: 55 AN: 32926

Ashkenazi Jewish (ASJ) AF: 0.00217 AC: 52 AN: 24002

East Asian (EAS) AF: 0.00 AC: 0 AN: 32258

South Asian (SAS) AF: 0.00 AC: 0 AN: 76774

European-Finnish (FIN) AF: 0.00975 AC: 384 AN: 39394

Middle Eastern (MID) AF: 0.000446 AC: 2 AN: 4482

European-Non Finnish (NFE) AF: 0.00538 AC: 5750 AN: 1067968

Other (OTH) AF: 0.00290 AC: 164 AN: 56628

GnomAD4 genome AF: 0.00347 AC: 527 AN: 151798 Hom.: 1 Cov.: 32 AF XY: 0.00369 AC XY: 274 AN XY: 74210

African (AFR) AF: 0.000844 AC: 35 AN: 41484

American (AMR) AF: 0.00216 AC: 33 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00261 AC: 9 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00930 AC: 98 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00515 AC: 349 AN: 67788

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.00225 Hom.: 1

Bravo AF: 0.00276

ExAC AF: 0.000576 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.46
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.050
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.035	D
Polyphen		0.0020	B
Vest4		0.31
MVP		0.043
MPC		0.69
ClinPred		0.11	T
GERP RS		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.13
Mutation Taster		=98/2	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: rs573842562; hg19: chr8-81399185;