6-130051261-A-G

Variant names:

• chr6-130051261-A-G
• NM_032438.4:c.302A>G

Variant summary

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

The NM_032438.4(L3MBTL3):​c.302A>G​(p.Lys101Arg) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: L3MBTL3 NM_032438.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27

Genes affected

L3MBTL3 (HGNC:23035): (L3MBTL histone methyl-lysine binding protein 3) This gene encodes a member of the malignant brain tumor (MBT) family of chromatin interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. The encoded protein may regulate hematopoiesis. Homozygous deletion of this gene has been observed in human patients with medulloblastoma. [provided by RefSeq, Oct 2016]

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=0.26102537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.302A>G	p.Lys101Arg	missense_variant	Exon 6 of 23	ENST00000361794.7	NP_115814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.302A>G	p.Lys101Arg	missense_variant	Exon 6 of 23	5	NM_032438.4	ENSP00000354526.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302A>G (p.K101R) alteration is located in exon 6 (coding exon 4) of the L3MBTL3 gene. This alteration results from a A to G substitution at nucleotide position 302, causing the lysine (K) at amino acid position 101 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;T;T;.;T;.;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.86	.;D;D;.;D;.;D;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.1	M;.;M;.;.;.;.;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.81	N;N;N;N;N;N;N;N
REVEL	Benign	0.098
Sift	Uncertain	0.016	D;D;D;T;D;T;T;D
Sift4G	Benign	0.43	T;D;T;T;D;T;T;T
Polyphen		0.97	D;.;D;D;.;D;D;D
Vest4		0.45
MutPred		0.16		Loss of ubiquitination at K101 (P = 0.0047);.;Loss of ubiquitination at K101 (P = 0.0047);.;Loss of ubiquitination at K101 (P = 0.0047);.;.;Loss of ubiquitination at K101 (P = 0.0047);
MVP		0.67
MPC		0.78
ClinPred		0.69	D
GERP RS		5.0
Varity_R		0.15
gMVP		0.26

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: chr6-130372406;