6-130132697-C-T

Variant names:

• chr6-130132697-C-T
• rs3777428
• NM_032438.4:c.1967-755C>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.1967-755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,948 control chromosomes in the GnomAD database, including 2,155 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 0.13 (2155 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL3	NM_032438.4	MANE Select	c.1967-755C>T		intron	N/A	NP_115814.1	Q96JM7-1
	L3MBTL3	NM_001007102.4		c.1892-755C>T		intron	N/A	NP_001007103.1	Q96JM7-2
	L3MBTL3	NM_001346550.2		c.1892-755C>T		intron	N/A	NP_001333479.1	Q96JM7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL3	ENST00000361794.7	TSL:5 MANE Select	c.1967-755C>T		intron	N/A	ENSP00000354526.2	Q96JM7-1
	L3MBTL3	ENST00000533560.5	TSL:1	c.1892-755C>T		intron	N/A	ENSP00000437185.1	Q96JM7-2
	L3MBTL3	ENST00000858931.1		c.2072-755C>T		intron	N/A	ENSP00000528990.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19617 AN: 151836 Hom.: 2146 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.129 AC: 19655 AN: 151948 Hom.: 2155 Cov.: 32 AF XY: 0.129 AC XY: 9601 AN XY: 74282

African (AFR) AF: 0.289 AC: 11942 AN: 41378

American (AMR) AF: 0.155 AC: 2367 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3468

East Asian (EAS) AF: 0.0904 AC: 468 AN: 5176

South Asian (SAS) AF: 0.113 AC: 542 AN: 4800

European-Finnish (FIN) AF: 0.0232 AC: 244 AN: 10534

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0488 AC: 3319 AN: 67996

Other (OTH) AF: 0.130 AC: 275 AN: 2110

Alfa AF: 0.0678 Hom.: 882

Bravo AF: 0.146

Asia WGS AF: 0.134 AC: 469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.72
PhyloP100		-0.0040
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: rs3777428; hg19: chr6-130453842;