rs762517126

Variant names:

• chr18-5969469-C-G
• rs762517126
• NM_001330559.2:c.1538G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-5969469-C-G
• chr18-5969469-C-T

Variant summary

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

The NM_001330559.2(L3MBTL4):​c.1538G>C​(p.Arg513Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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. R513K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: L3MBTL4 NM_001330559.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL4	NM_001330559.2	c.1538G>C	p.Arg513Thr	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.1538G>C	p.Arg513Thr	missense_variant	Exon 17 of 19	5	NM_001330559.2	ENSP00000318543.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.41	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.049	D;T
Polyphen		0.98	D;D
Vest4		0.50
MutPred		0.39		Loss of solvent accessibility (P = 0.0155);.;
MVP		0.41
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.11
gMVP		0.31
Mutation Taster		=90/10	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: rs762517126; hg19: chr18-5969468;