6-130027974-C-T

Variant names:

• chr6-130027974-C-T
• rs6569648
• NM_032438.4:c.-16+5669C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 111 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=-0.89).
• 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 rank	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.-16+5669C>T		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.-16+5669C>T		intron_variant	Intron 2 of 22	5	NM_032438.4	ENSP00000354526.2

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

African (AFR) AF: 0.963 AC: 39990 AN: 41542

American (AMR) AF: 0.871 AC: 13300 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2904 AN: 3466

East Asian (EAS) AF: 0.940 AC: 4867 AN: 5180

South Asian (SAS) AF: 0.880 AC: 4243 AN: 4824

European-Finnish (FIN) AF: 0.783 AC: 8255 AN: 10540

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.766 AC: 52015 AN: 67948

Other (OTH) AF: 0.852 AC: 1797 AN: 2108

Alfa AF: 0.795 Hom.: 219188

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
PhyloP100		-0.39
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: rs6569648; hg19: chr6-130349119;