16-11838073-C-T

Variant names:

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

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>A​(p.Ser396Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,445,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S396I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RSL1D1 NM_015659.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.12907699).

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>A	p.Ser396Asn	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>A	p.Ser396Asn	missense	Exon 9 of 9	ENSP00000460871.1	O76021-1
	RSL1D1	ENST00000355674.9	TSL:1	c.1184G>A	p.Ser395Asn	missense	Exon 9 of 9	ENSP00000347897.5	J3QSV6
	RSL1D1	ENST00000898748.1		c.1214G>A	p.Ser405Asn	missense	Exon 9 of 9	ENSP00000568807.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000131 AC: 3 AN: 229326 AF XY: 0.0000241

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000484 AC: 7 AN: 1445946 Hom.: 0 Cov.: 31 AF XY: 0.00000974 AC XY: 7 AN XY: 718896

African (AFR) AF: 0.00 AC: 0 AN: 32162

American (AMR) AF: 0.0000251 AC: 1 AN: 39920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25394

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 82050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1108200

Other (OTH) AF: 0.00 AC: 0 AN: 59692

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.12
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.047
Sift	Benign	0.039	D
Sift4G	Uncertain	0.052	T
Polyphen		0.96	P
Vest4		0.10
MutPred		0.17		Loss of phosphorylation at S396 (P = 0.0063)
MVP		0.64
MPC		0.063
ClinPred		0.16	T
GERP RS		1.7
Varity_R		0.030
gMVP		0.10

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;