rs765233692

Variant names:

• chr18-5969482-G-A
• rs765233692
• NM_001330559.2:c.1525C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-5969482-G-A
• chr18-5969482-G-C

Variant summary

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

The NM_001330559.2(L3MBTL4):​c.1525C>T​(p.Leu509Phe) 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. 12/21 in silico tools predict 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. L509V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: L3MBTL4 NM_001330559.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29
• Publications: 0 publications found

Genes affected

L3MBTL4 (HGNC:26677): (L3MBTL histone methyl-lysine binding protein 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000266846 (HGNC:):

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=0.19536322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.1525C>T	p.Leu509Phe	missense_variant	Exon 17 of 19	ENST00000317931.12	NP_001317488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL4	ENST00000317931.12	c.1525C>T	p.Leu509Phe	missense_variant	Exon 17 of 19	5	NM_001330559.2	ENSP00000318543.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249278 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	0.046
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		5.3
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.069
Sift	Benign	0.090	T;T
Sift4G	Benign	0.087	T;T
Polyphen		0.16	B;B
Vest4		0.35
MutPred		0.42		Loss of disorder (P = 0.1918);.;
MVP		0.39
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs765233692; hg19: chr18-5969481;