rs550972691

Variant names:

• chr16-11838113-T-C
• rs550972691
• NM_015659.3:c.1147A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-11838113-T-C
• chr16-11838113-T-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015659.3(RSL1D1):​c.1147A>G​(p.Ile383Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,556,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RSL1D1 NM_015659.3 missense, splice_region
• Scores: Splicing: ADA: 0.00002929
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.239
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016940773).

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.1147A>G	p.Ile383Val	missense splice_region	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.1147A>G	p.Ile383Val	missense splice_region	Exon 9 of 9	ENSP00000460871.1	O76021-1
	RSL1D1	ENST00000355674.9	TSL:1	c.1144A>G	p.Ile382Val	missense splice_region	Exon 9 of 9	ENSP00000347897.5	J3QSV6
	RSL1D1	ENST00000898748.1		c.1174A>G	p.Ile392Val	missense splice_region	Exon 9 of 9	ENSP00000568807.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151192 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000494 AC: 1 AN: 202346 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: 0.0000636

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405642 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 696224

African (AFR) AF: 0.00 AC: 0 AN: 30342

American (AMR) AF: 0.00 AC: 0 AN: 30406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23212

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39044

South Asian (SAS) AF: 0.00 AC: 0 AN: 77724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090214

Other (OTH) AF: 0.00 AC: 0 AN: 57664

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151310 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73920

African (AFR) AF: 0.00 AC: 0 AN: 41144

American (AMR) AF: 0.00 AC: 0 AN: 15182

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67838

Other (OTH) AF: 0.00 AC: 0 AN: 2104

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	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.76
DANN	Benign	0.20
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.29	N
PhyloP100		-0.24
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.017
Sift	Benign	0.99	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.033
MutPred		0.28		Loss of helix (P = 0.1299)
MVP		0.11
MPC		0.012
ClinPred		0.013	T
GERP RS		-5.6
Varity_R		0.0093
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.022
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: rs550972691; hg19: chr16-11931970;