6-42880949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366481.3(RPL7L1):c.130C>T(p.Leu44Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000126 in 1,426,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: RPL7L1 NM_001366481.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71

Genes affected

RPL7L1 (HGNC:21370): (ribosomal protein L7 like 1) Enables RNA binding activity. Predicted to be involved in maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to act upstream of or within blastocyst formation. Predicted to be located in nucleolus. Predicted to be part of cytosolic large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33795607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL7L1	NM_001366481.3	c.130C>T	p.Leu44Phe	missense_variant	2/6	ENST00000493763.7
RPL7L1	NM_198486.5	c.130C>T	p.Leu44Phe	missense_variant	2/7
RPL7L1	NR_134562.3	n.425C>T		non_coding_transcript_exon_variant	2/7
RPL7L1	NR_134563.3	n.336+998C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL7L1	ENST00000493763.7	c.130C>T	p.Leu44Phe	missense_variant	2/6	1	NM_001366481.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000280 AC: 7 AN: 249738 Hom.: 0 AF XY: 0.0000296 AC XY: 4 AN XY: 135272

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000126 AC: 18 AN: 1426974 Hom.: 0 Cov.: 23 AF XY: 0.00000843 AC XY: 6 AN XY: 712142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.00000925

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.103C>T (p.L35F) alteration is located in exon 2 (coding exon 2) of the RPL7L1 gene. This alteration results from a C to T substitution at nucleotide position 103, causing the leucine (L) at amino acid position 35 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.56	T
REVEL	Uncertain	0.33
MVP		0.58
MPC		1.1
ClinPred		0.94	D
GERP RS		4.8
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs780089884; hg19: chr6-42848687;