8-80486900-C-A

Variant names:

• chr8-80486900-C-A
• rs1221938119
• NM_001105539.3:c.90C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105539.3(ZBTB10):​c.90C>A​(p.Asn30Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,514,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• 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]

ENSG00000251867 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2217452).

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.90C>A	p.Asn30Lys	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
	ZBTB10	NM_023929.5		c.90C>A	p.Asn30Lys	missense	Exon 1 of 7	NP_076418.3
	ZBTB10	NM_001277145.2		c.96+1021C>A		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.90C>A	p.Asn30Lys	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
	ZBTB10	ENST00000430430.5	TSL:5	c.90C>A	p.Asn30Lys	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
	ZBTB10	ENST00000961791.1		c.90C>A	p.Asn30Lys	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151698 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000958 AC: 1 AN: 104330 AF XY: 0.00

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: 0.0000282

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 27 AN: 1362744 Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 12 AN XY: 671924

African (AFR) AF: 0.00 AC: 0 AN: 27598

American (AMR) AF: 0.00 AC: 0 AN: 32754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23926

East Asian (EAS) AF: 0.00 AC: 0 AN: 31502

South Asian (SAS) AF: 0.00 AC: 0 AN: 76378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.0000234 AC: 25 AN: 1066470

Other (OTH) AF: 0.0000354 AC: 2 AN: 56514

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151698 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67840

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000469 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T
Eigen	Benign	0.055
Eigen_PC	Benign	-0.0048
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.091
Sift	Uncertain	0.011	D
Sift4G	Benign	0.42	T
Polyphen		0.98	D
Vest4		0.22
MutPred		0.18		Gain of ubiquitination at N30 (P = 0.0069)
MVP		0.043
MPC		0.85
ClinPred		0.45	T
GERP RS		2.0
Varity_R		0.13
gMVP		0.11
Mutation Taster		=91/9	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: rs1221938119; hg19: chr8-81399135;