NM_032438.4:c.1966+2021C>T

Variant names:

• chr6-130122979-C-T
• rs10485400
• NM_032438.4:c.1966+2021C>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.1966+2021C>T 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 151,986 control chromosomes in the GnomAD database, including 16,557 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 (16557 hom., cov: 33)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.73 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.1966+2021C>T		intron	N/A	NP_115814.1
	L3MBTL3	NM_001007102.4		c.1891+2021C>T		intron	N/A	NP_001007103.1
	L3MBTL3	NM_001346550.2		c.1891+2021C>T		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.1966+2021C>T		intron	N/A	ENSP00000354526.2
	L3MBTL3	ENST00000533560.5	TSL:1	c.1891+2021C>T		intron	N/A	ENSP00000437185.1
	L3MBTL3	ENST00000368136.3	TSL:5	c.1966+2021C>T		intron	N/A	ENSP00000357118.2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66250 AN: 151870 Hom.: 16564 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.436 AC: 66259 AN: 151986 Hom.: 16557 Cov.: 33 AF XY: 0.444 AC XY: 32972 AN XY: 74278

African (AFR) AF: 0.184 AC: 7618 AN: 41436

American (AMR) AF: 0.523 AC: 7994 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2161 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3872 AN: 5166

South Asian (SAS) AF: 0.538 AC: 2595 AN: 4822

European-Finnish (FIN) AF: 0.573 AC: 6037 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34379 AN: 67954

Other (OTH) AF: 0.469 AC: 988 AN: 2108

Alfa AF: 0.450 Hom.: 6314

Bravo AF: 0.423

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.59
PhyloP100		-1.6
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: rs10485400; hg19: chr6-130444124; COSMIC: COSV62388626;