NM_001376113.1:c.1246G>C

Variant names:

• chr3-141443634-G-C
• NM_001376113.1:c.1246G>C
• ZBTB38 p.Gly416Arg

Variant summary

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

The NM_001376113.1(ZBTB38):​c.1246G>C​(p.Gly416Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB38 NM_001376113.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• Publications: 0 publications found

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]

ENSG00000288585 (HGNC:):

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=0.23545405).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376113.1. 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
	ZBTB38	NM_001376113.1	MANE Select	c.1246G>C	p.Gly416Arg	missense	Exon 6 of 6	NP_001363042.1	Q8NAP3
	ZBTB38	NM_001080412.3		c.1246G>C	p.Gly416Arg	missense	Exon 8 of 8	NP_001073881.2	Q8NAP3
	ZBTB38	NM_001350099.2		c.1246G>C	p.Gly416Arg	missense	Exon 6 of 6	NP_001337028.1	Q8NAP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB38	ENST00000321464.7	TSL:6 MANE Select	c.1246G>C	p.Gly416Arg	missense	Exon 6 of 6	ENSP00000372635.5	Q8NAP3
	ZBTB38	ENST00000509883.5	TSL:1	c.1246G>C	p.Gly416Arg	missense	Exon 3 of 3	ENSP00000424254.1	D6RBC4
	ZBTB38	ENST00000441582.2	TSL:2	c.1246G>C	p.Gly416Arg	missense	Exon 2 of 2	ENSP00000406955.2	Q8NAP3

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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.038	D
Sift4G	Benign	0.098	T
Varity_R		0.090
gMVP		0.38
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-141162476;