3-141443760-A-G

Position:

• chr3-141443760-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001376113.1(ZBTB38):​c.1372A>G​(p.Met458Val) 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. 15/21 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: ZBTB38 NM_001376113.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

Genes affected

ZBTB38 (HGNC:26636): (zinc finger and BTB domain containing 38) The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZBTB38
• BP4: Computational evidence support a benign effect (MetaRNN=0.10747701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB38	NM_001376113.1	c.1372A>G	p.Met458Val	missense_variant	6/6	ENST00000321464.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB38	ENST00000321464.7	c.1372A>G	p.Met458Val	missense_variant	6/6		NM_001376113.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Dec 08, 2023

The c.1372A>G (p.M458V) alteration is located in exon 8 (coding exon 1) of the ZBTB38 gene. This alteration results from a A to G substitution at nucleotide position 1372, causing the methionine (M) at amino acid position 458 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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.41
DEOGEN2	Benign	0.0036	T;.;T;T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.64	T;T;.;.;.;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.44	T
Polyphen		0.0020	.;.;B;B;B;B
Vest4		0.16, 0.16, 0.16
MutPred		0.60		Loss of catalytic residue at V454 (P = 0.0588);Loss of catalytic residue at V454 (P = 0.0588);Loss of catalytic residue at V454 (P = 0.0588);Loss of catalytic residue at V454 (P = 0.0588);Loss of catalytic residue at V454 (P = 0.0588);Loss of catalytic residue at V454 (P = 0.0588);
MVP		0.082
MPC		0.42
ClinPred		0.43	T
GERP RS		4.4
Varity_R		0.078
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-141162602;