6-130027974-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.-16+5669C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,086 control chromosomes in the GnomAD database, including 54,677 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 0.84 (54677 hom., cov: 31)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L3MBTL3	NM_032438.4	c.-16+5669C>T		intron_variant		ENST00000361794.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.-16+5669C>T		intron_variant		5	NM_032438.4	A1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128093 AN: 151968 Hom.: 54606 Cov.: 31

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.843 AC: 128225 AN: 152086 Hom.: 54677 Cov.: 31 AF XY: 0.846 AC XY: 62885 AN XY: 74362

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.871

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.852

Alfa AF: 0.787 Hom.: 102863

Bravo AF: 0.854

Asia WGS AF: 0.924 AC: 3202 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.87
Dann	Benign	0.55

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: rs6569648; hg19: chr6-130349119;