NM_015659.3:c.1432A>G

Variant names:

• chr16-11837828-T-C
• rs563090505
• NM_015659.3:c.1432A>G

Variant summary

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

The NM_015659.3(RSL1D1):​c.1432A>G​(p.Lys478Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. K478Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RSL1D1 NM_015659.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• Publications: 0 publications found

Genes affected

RSL1D1 (HGNC:24534): (ribosomal L1 domain containing 1) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Involved in regulation of apoptotic process and regulation of cellular senescence. Acts upstream of or within regulation of protein localization. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17085606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015659.3. 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
	RSL1D1	NM_015659.3	MANE Select	c.1432A>G	p.Lys478Glu	missense	Exon 9 of 9	NP_056474.2	O76021-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSL1D1	ENST00000571133.6	TSL:1 MANE Select	c.1432A>G	p.Lys478Glu	missense	Exon 9 of 9	ENSP00000460871.1	O76021-1
	RSL1D1	ENST00000898748.1		c.1459A>G	p.Lys487Glu	missense	Exon 9 of 9	ENSP00000568807.1
	RSL1D1	ENST00000927449.1		c.1429A>G	p.Lys477Glu	missense	Exon 9 of 9	ENSP00000597508.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458938 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725632

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110940

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.0038
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.085	T
Polyphen		0.94	P
Vest4		0.25
MutPred		0.24		Loss of methylation at K478 (P = 0.002)
MVP		0.54
MPC		0.014
ClinPred		0.50	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.048
Mutation Taster		=88/12	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: rs563090505; hg19: chr16-11931685;