3-141442467-C-G

Position:

• chr3-141442467-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001376113.1(ZBTB38):​c.79C>G​(p.Arg27Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.57

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.79C>G	p.Arg27Gly	missense_variant	6/6	ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.79C>G	p.Arg27Gly	missense_variant	6/6		NM_001376113.1	ENSP00000372635	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 07, 2022

The c.79C>G (p.R27G) alteration is located in exon 8 (coding exon 1) of the ZBTB38 gene. This alteration results from a C to G substitution at nucleotide position 79, causing the arginine (R) at amino acid position 27 to be replaced by a glycine (G). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.;T;T;.;.;D;D;D;D;.;D;.;D;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;.;.;D;D;D;.;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.62	D
MutationAssessor	Pathogenic	4.2	.;.;.;.;.;.;H;H;.;.;.;H;.;.;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.0	D;D;.;D;D;D;D;.;D;D;D;D;D;D;.
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D;D;.;D;D;D;D;.;D;D;D;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;.;D;D;D;D;.;D;D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;.;.;D;D;.;.;.;D;.;.;D
Vest4		0.84, 0.88, 0.88
MutPred		0.78		Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);Loss of solvent accessibility (P = 0.1434);
MVP		0.78
MPC		1.4
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.92
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-141161309;