16-11838073-C-A

Variant names:

• chr16-11838073-C-A
• rs771611819
• NM_015659.3:c.1187G>T

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.1187G>T​(p.Ser396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RSL1D1 NM_015659.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.119
• 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=0.17660567).

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.1187G>T	p.Ser396Ile	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.1187G>T	p.Ser396Ile	missense	Exon 9 of 9	ENSP00000460871.1	O76021-1
	RSL1D1	ENST00000355674.9	TSL:1	c.1184G>T	p.Ser395Ile	missense	Exon 9 of 9	ENSP00000347897.5	J3QSV6
	RSL1D1	ENST00000898748.1		c.1214G>T	p.Ser405Ile	missense	Exon 9 of 9	ENSP00000568807.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.073
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.12
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.064
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.020	D
Polyphen		0.95	P
Vest4		0.17
MutPred		0.18		Loss of phosphorylation at S396 (P = 0.0063)
MVP		0.67
MPC		0.073
ClinPred		0.70	D
GERP RS		1.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.052
gMVP		0.26

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: rs771611819; hg19: chr16-11931930;