6-130052980-G-T

Variant names:

• chr6-130052980-G-T
• rs755432504
• NM_032438.4:c.571G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032438.4(L3MBTL3):​c.571G>T​(p.Asp191Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D191N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: L3MBTL3 NM_032438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2005058).

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.571G>T	p.Asp191Tyr	missense	Exon 7 of 23	NP_115814.1	Q96JM7-1
	L3MBTL3	NM_001007102.4		c.496G>T	p.Asp166Tyr	missense	Exon 6 of 22	NP_001007103.1	Q96JM7-2
	L3MBTL3	NM_001346550.2		c.496G>T	p.Asp166Tyr	missense	Exon 6 of 22	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.571G>T	p.Asp191Tyr	missense	Exon 7 of 23	ENSP00000354526.2	Q96JM7-1
	L3MBTL3	ENST00000533560.5	TSL:1	c.496G>T	p.Asp166Tyr	missense	Exon 6 of 22	ENSP00000437185.1	Q96JM7-2
	L3MBTL3	ENST00000858931.1		c.676G>T	p.Asp226Tyr	missense	Exon 7 of 23	ENSP00000528990.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.070
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.011	D
Polyphen		0.48	P
Vest4		0.42
MutPred		0.26		Gain of loop (P = 0.0013)
MVP		0.33
MPC		0.58
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.38
Mutation Taster		=66/34	polymorphism

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: rs755432504; hg19: chr6-130374125;