rs6899976

Variant names:

• chr6-130037283-G-A
• rs6899976
• NM_032438.4:c.-15-5402G>A

Variant summary

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

The NM_032438.4(L3MBTL3):​c.-15-5402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,988 control chromosomes in the GnomAD database, including 28,199 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 0.57 (28199 hom., cov: 31)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 25 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.-15-5402G>A		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.-15-5402G>A		intron_variant	Intron 2 of 22	5	NM_032438.4	ENSP00000354526.2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86359 AN: 151870 Hom.: 28191 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.568 AC: 86388 AN: 151988 Hom.: 28199 Cov.: 31 AF XY: 0.574 AC XY: 42597 AN XY: 74274

African (AFR) AF: 0.222 AC: 9190 AN: 41444

American (AMR) AF: 0.647 AC: 9880 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2653 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3938 AN: 5174

South Asian (SAS) AF: 0.629 AC: 3027 AN: 4816

European-Finnish (FIN) AF: 0.745 AC: 7864 AN: 10562

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47792 AN: 67956

Other (OTH) AF: 0.622 AC: 1307 AN: 2100

Alfa AF: 0.672 Hom.: 154372

Bravo AF: 0.549

Asia WGS AF: 0.649 AC: 2248 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.35
PhyloP100		-0.49
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: rs6899976; hg19: chr6-130358428;