6-33455438-A-T

Variant names:

• chr6-33455438-A-T
• rs1307702910
• NM_152735.4:c.338A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152735.4(ZBTB9):​c.338A>T​(p.Asp113Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB9 NM_152735.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB9	NM_152735.4	c.338A>T	p.Asp113Val	missense_variant	Exon 2 of 2	ENST00000395064.3	NP_689948.1
ZBTB9	XM_047418350.1	c.338A>T	p.Asp113Val	missense_variant	Exon 2 of 2		XP_047274306.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB9	ENST00000395064.3	c.338A>T	p.Asp113Val	missense_variant	Exon 2 of 2	1	NM_152735.4	ENSP00000378503.2
ZBTB9	ENST00000621915.1	c.338A>T	p.Asp113Val	missense_variant	Exon 2 of 2	4		ENSP00000484265.1
ZBTB9	ENST00000612407.1	c.32A>T	p.Asp11Val	missense_variant	Exon 1 of 2	3		ENSP00000478118.1
ZBTB9	ENST00000612775.1	c.*101A>T		downstream_gene_variant		4		ENSP00000484571.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.338A>T (p.D113V) alteration is located in exon 2 (coding exon 1) of the ZBTB9 gene. This alteration results from a A to T substitution at nucleotide position 338, causing the aspartic acid (D) at amino acid position 113 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	.;N
REVEL	Uncertain	0.32
Sift	Benign	0.048	.;D
Sift4G	Benign	0.074	T;D
Polyphen		0.97	.;D
Vest4		0.47
MutPred		0.47		Gain of methylation at R109 (P = 0.0943);Gain of methylation at R109 (P = 0.0943);
MVP		0.90
MPC		1.2
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.24
gMVP		0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1307702910; hg19: chr6-33423215;