rs563090505

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-11837828-T-G
• chr16-11837828-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015659.3(RSL1D1):​c.1432A>C​(p.Lys478Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000751 in 1,611,140 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K478N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: RSL1D1 NM_015659.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07214412).

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>C	p.Lys478Gln	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>C	p.Lys478Gln	missense	Exon 9 of 9	ENSP00000460871.1	O76021-1
	RSL1D1	ENST00000898748.1		c.1459A>C	p.Lys487Gln	missense	Exon 9 of 9	ENSP00000568807.1
	RSL1D1	ENST00000927449.1		c.1429A>C	p.Lys477Gln	missense	Exon 9 of 9	ENSP00000597508.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152086 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000128 AC: 32 AN: 249116 AF XY: 0.000149

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.0000590

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000219

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000665 AC: 97 AN: 1458936 Hom.: 0 Cov.: 31 AF XY: 0.0000717 AC XY: 52 AN XY: 725630

African (AFR) AF: 0.000483 AC: 16 AN: 33134

American (AMR) AF: 0.0000455 AC: 2 AN: 43962

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

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39672

South Asian (SAS) AF: 0.000350 AC: 30 AN: 85800

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

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1110940

Other (OTH) AF: 0.000183 AC: 11 AN: 60250

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152204 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16 AN XY: 74426

African (AFR) AF: 0.000458 AC: 19 AN: 41530

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000219 Hom.: 0

Bravo AF: 0.000298

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.0067
Eigen_PC	Benign	-0.063
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.079	T
Polyphen		0.98	D
Vest4		0.20
MVP		0.55
MPC		0.012
ClinPred		0.048	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.061
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;