6-130132697-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032438.4(L3MBTL3):c.1967-755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,948 control chromosomes in the GnomAD database, including 2,155 homozygotes. 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: 𝑓 0.13 (2155 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L3MBTL3	NM_032438.4	c.1967-755C>T		intron_variant		ENST00000361794.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.1967-755C>T		intron_variant		5	NM_032438.4	A1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19617 AN: 151836 Hom.: 2146 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19655 AN: 151948 Hom.: 2155 Cov.: 32 AF XY: 0.129 AC XY: 9601 AN XY: 74282

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0904

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0488

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0638 Hom.: 644

Bravo AF: 0.146

Asia WGS AF: 0.134 AC: 469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.9
Dann	Benign	0.72

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: rs3777428; hg19: chr6-130453842;