9-126833092-C-G

Position:

• chr9-126833092-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014007.4(ZBTB43):​c.583C>G​(p.Leu195Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB43 NM_014007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.852

Genes affected

ZBTB43 (HGNC:17908): (zinc finger and BTB domain containing 43) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13966525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB43	NM_014007.4	c.583C>G	p.Leu195Val	missense_variant	3/3	ENST00000373464.5	NP_054726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB43	ENST00000373464.5	c.583C>G	p.Leu195Val	missense_variant	3/3	1	NM_014007.4	ENSP00000362563	P1
ZBTB43	ENST00000373457.1	c.583C>G	p.Leu195Val	missense_variant	1/1			ENSP00000362556	P1
ZBTB43	ENST00000449886.5	c.583C>G	p.Leu195Val	missense_variant	2/2	3		ENSP00000390344	P1
ZBTB43	ENST00000450858.1	c.583C>G	p.Leu195Val	missense_variant	2/2	3		ENSP00000412145

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.583C>G (p.L195V) alteration is located in exon 3 (coding exon 1) of the ZBTB43 gene. This alteration results from a C to G substitution at nucleotide position 583, causing the leucine (L) at amino acid position 195 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	Benign	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.022	T;T;T;T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.75	T;.;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.90	L;L;.;L
MutationTaster	Benign	0.87	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.14	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;D;T
Sift4G	Benign	0.56	T;T;D;T
Polyphen		0.88	P;P;.;P
Vest4		0.16
MutPred		0.077		Gain of glycosylation at S197 (P = 0.1505);Gain of glycosylation at S197 (P = 0.1505);Gain of glycosylation at S197 (P = 0.1505);Gain of glycosylation at S197 (P = 0.1505);
MVP		0.13
MPC		0.79
ClinPred		0.21	T
GERP RS		3.8
Varity_R		0.097
gMVP		0.45

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: rs868178594; hg19: chr9-129595371;