rs9321208

Positions:

• chr6-130112145-G-A
• chr6-130112145-G-C
• chr6-130112145-G-T

Variant summary

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

The NM_032438.4(L3MBTL3):​c.1886+7570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,102 control chromosomes in the GnomAD database, including 5,115 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 0.23 (5115 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.1886+7570G>A		intron_variant		ENST00000361794.7	NP_115814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.1886+7570G>A		intron_variant		5	NM_032438.4	ENSP00000354526	A1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34810 AN: 151984 Hom.: 5116 Cov.: 32

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.229 AC: 34807 AN: 152102 Hom.: 5115 Cov.: 32 AF XY: 0.225 AC XY: 16714 AN XY: 74376

Gnomad4 AFR AF: 0.0767

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.225

Alfa AF: 0.303 Hom.: 10730

Bravo AF: 0.213

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.75

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: rs9321208; hg19: chr6-130433290;