6-130136933-C-A

Variant names:

• chr6-130136933-C-A
• rs4897366
• NM_032438.4:c.2200-2677C>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.2200-2677C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,066 control chromosomes in the GnomAD database, including 16,530 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 0.44 (16530 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 4 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]

ENSG00000227678 (HGNC:):

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 = 0.729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032438.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL3	NM_032438.4	MANE Select	c.2200-2677C>A		intron	N/A	NP_115814.1
	L3MBTL3	NM_001007102.4		c.2125-2677C>A		intron	N/A	NP_001007103.1
	L3MBTL3	NM_001346550.2		c.2125-2677C>A		intron	N/A	NP_001333479.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL3	ENST00000361794.7	TSL:5 MANE Select	c.2200-2677C>A		intron	N/A	ENSP00000354526.2
	L3MBTL3	ENST00000533560.5	TSL:1	c.2125-2677C>A		intron	N/A	ENSP00000437185.1
	L3MBTL3	ENST00000368136.3	TSL:5	c.2200-2677C>A		intron	N/A	ENSP00000357118.2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66270 AN: 151948 Hom.: 16536 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.436 AC: 66280 AN: 152066 Hom.: 16530 Cov.: 32 AF XY: 0.444 AC XY: 32995 AN XY: 74330

African (AFR) AF: 0.185 AC: 7685 AN: 41484

American (AMR) AF: 0.535 AC: 8178 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3468

East Asian (EAS) AF: 0.749 AC: 3867 AN: 5166

South Asian (SAS) AF: 0.539 AC: 2597 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6023 AN: 10560

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34275 AN: 67986

Other (OTH) AF: 0.471 AC: 992 AN: 2108

Alfa AF: 0.475 Hom.: 3248

Bravo AF: 0.424

Asia WGS AF: 0.595 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		-0.061
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: rs4897366; hg19: chr6-130458078;