6-33455786-C-A

Variant names:

• chr6-33455786-C-A
• rs778944081
• NM_152735.4:c.686C>A

Variant summary

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

The NM_152735.4(ZBTB9):​c.686C>A​(p.Ala229Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A229V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB9 NM_152735.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

ZBTB9 (HGNC:28323): (zinc finger and BTB domain containing 9) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=0.06955439).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152735.4. 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
	ZBTB9	NM_152735.4	MANE Select	c.686C>A	p.Ala229Asp	missense	Exon 2 of 2	NP_689948.1	Q96C00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB9	ENST00000395064.3	TSL:1 MANE Select	c.686C>A	p.Ala229Asp	missense	Exon 2 of 2	ENSP00000378503.2	Q96C00
	ZBTB9	ENST00000932373.1		c.686C>A	p.Ala229Asp	missense	Exon 2 of 2	ENSP00000602432.1
	ZBTB9	ENST00000932374.1		c.686C>A	p.Ala229Asp	missense	Exon 2 of 2	ENSP00000602433.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.029
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.22	B
Vest4		0.15
MutPred		0.27		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.30
MPC		0.58
ClinPred		0.11	T
GERP RS		4.4
PromoterAI		-0.020	Neutral
Varity_R		0.23
gMVP		0.21
Mutation Taster		=86/14	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: rs778944081; hg19: chr6-33423563;