6-130033710-T-C

Variant names:

• chr6-130033710-T-C
• rs9388766
• NM_032438.4:c.-15-8975T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032438.4(L3MBTL3):​c.-15-8975T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,132 control chromosomes in the GnomAD database, including 33,085 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 0.65 (33085 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.-15-8975T>C		intron_variant	Intron 2 of 22	ENST00000361794.7	NP_115814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.-15-8975T>C		intron_variant	Intron 2 of 22	5	NM_032438.4	ENSP00000354526.2

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98829 AN: 152014 Hom.: 33062 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.650 AC: 98895 AN: 152132 Hom.: 33085 Cov.: 32 AF XY: 0.653 AC XY: 48593 AN XY: 74378

African (AFR) AF: 0.485 AC: 20120 AN: 41480

American (AMR) AF: 0.697 AC: 10662 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2708 AN: 3468

East Asian (EAS) AF: 0.842 AC: 4355 AN: 5174

South Asian (SAS) AF: 0.636 AC: 3070 AN: 4828

European-Finnish (FIN) AF: 0.744 AC: 7872 AN: 10584

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47894 AN: 67986

Other (OTH) AF: 0.693 AC: 1466 AN: 2116

Alfa AF: 0.694 Hom.: 164506

Bravo AF: 0.644

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9388766; hg19: chr6-130354855;