8-80487052-C-T

Variant names:

• chr8-80487052-C-T
• rs542715037
• NM_001105539.3:c.242C>T

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.242C>T​(p.Ala81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000396 in 1,517,066 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. 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. A81D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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: 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=0.09193066).

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.242C>T	p.Ala81Val	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
	ZBTB10	NM_023929.5		c.242C>T	p.Ala81Val	missense	Exon 1 of 7	NP_076418.3
	ZBTB10	NM_001277145.2		c.96+1173C>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.242C>T	p.Ala81Val	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
	ZBTB10	ENST00000430430.5	TSL:5	c.242C>T	p.Ala81Val	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
	ZBTB10	ENST00000961791.1		c.242C>T	p.Ala81Val	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151890 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000727

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: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1365066 Hom.: 0 Cov.: 34 AF XY: 0.00000148 AC XY: 1 AN XY: 673634

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

African (AFR) AF: 0.0000713 AC: 2 AN: 28038

American (AMR) AF: 0.00 AC: 0 AN: 33156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24204

East Asian (EAS) AF: 0.00 AC: 0 AN: 32972

South Asian (SAS) AF: 0.00 AC: 0 AN: 77476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5384

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071448

Other (OTH) AF: 0.00 AC: 0 AN: 56986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152000 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

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

African (AFR) AF: 0.0000725 AC: 3 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

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

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00383038), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.053
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.12	T
Polyphen		0.0080	B
Vest4		0.11
MutPred		0.17		Gain of sheet (P = 0.0477)
MVP		0.043
MPC		0.72
ClinPred		0.24	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.15
gMVP		0.098
Mutation Taster		=97/3	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: rs542715037; hg19: chr8-81399287;