16-11838113-T-A

Variant names:

• chr16-11838113-T-A
• rs550972691
• NM_015659.3:c.1147A>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.1147A>T​(p.Ile383Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000783 in 1,405,596 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. 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. I383V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000078 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSL1D1 NM_015659.3 missense, splice_region
• Scores: Splicing: ADA: 0.0002711
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.07043123).

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>T	p.Ile383Phe	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>T	p.Ile383Phe	missense splice_region	Exon 9 of 9	ENSP00000460871.1	O76021-1
	RSL1D1	ENST00000355674.9	TSL:1	c.1144A>T	p.Ile382Phe	missense splice_region	Exon 9 of 9	ENSP00000347897.5	J3QSV6
	RSL1D1	ENST00000898748.1		c.1174A>T	p.Ile392Phe	missense splice_region	Exon 9 of 9	ENSP00000568807.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151188 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: 0.00

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: 0.0000198 AC: 4 AN: 202346 AF XY: 0.00000899

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000417

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000783 AC: 11 AN: 1405596 Hom.: 0 Cov.: 30 AF XY: 0.00000718 AC XY: 5 AN XY: 696202

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000330 AC: 1 AN: 30328

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23210

East Asian (EAS) AF: 0.00 AC: 0 AN: 39044

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

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5438

European-Non Finnish (NFE) AF: 0.00000642 AC: 7 AN: 1090192

Other (OTH) AF: 0.0000347 AC: 2 AN: 57662

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000168754), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151188 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73790

African (AFR) AF: 0.00 AC: 0 AN: 41020

American (AMR) AF: 0.00 AC: 0 AN: 15162

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67846

Other (OTH) AF: 0.00 AC: 0 AN: 2082

EpiCase AF: 0.00

EpiControl AF: 0.000120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.71
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.24
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.083
Sift	Uncertain	0.025	D
Sift4G	Benign	0.12	T
Polyphen		0.58	P
Vest4		0.097
MutPred		0.31		Loss of MoRF binding (P = 0.0895)
MVP		0.20
MPC		0.016
ClinPred		0.10	T
GERP RS		-5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.050
SpliceAI score (max)		0.020		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;