6-42880926-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001366481.3(RPL7L1):c.107A>G(p.Lys36Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000639 in 1,607,242 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (2 hom.)
• Consequence: RPL7L1 NM_001366481.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.23

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03445065).
• BS2: High Homozygotes in GnomAdExome at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL7L1	NM_001366481.3	c.107A>G	p.Lys36Arg	missense_variant	2/6	ENST00000493763.7
RPL7L1	NM_198486.5	c.107A>G	p.Lys36Arg	missense_variant	2/7
RPL7L1	NR_134562.3	n.402A>G		non_coding_transcript_exon_variant	2/7
RPL7L1	NR_134563.3	n.336+975A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL7L1	ENST00000493763.7	c.107A>G	p.Lys36Arg	missense_variant	2/6	1	NM_001366481.3	P1

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 79 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000756 AC: 189 AN: 250018 Hom.: 2 AF XY: 0.000989 AC XY: 134 AN XY: 135518

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000651 AC: 947 AN: 1454878 Hom.: 2 Cov.: 26 AF XY: 0.000708 AC XY: 513 AN XY: 724220

Gnomad4 AFR exome AF: 0.0000900

Gnomad4 AMR exome AF: 0.000448

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000941

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000680

Gnomad4 OTH exome AF: 0.000582

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152364 Hom.: 0 Cov.: 32 AF XY: 0.000483 AC XY: 36 AN XY: 74510

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000764

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000822 Hom.: 0

Bravo AF: 0.000529

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000733 AC: 89

EpiCase AF: 0.00125

EpiControl AF: 0.00160

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

Oct 18, 2021

The c.80A>G (p.K27R) alteration is located in exon 2 (coding exon 2) of the RPL7L1 gene. This alteration results from a A to G substitution at nucleotide position 80, causing the lysine (K) at amino acid position 27 to be replaced by an arginine (R). 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	Benign	0.22
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	23
Dann	Uncertain	1.0
Eigen	Benign	0.059
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.68	T
REVEL	Benign	0.13
MVP		0.72
MPC		0.50
ClinPred		0.046	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs147359090; hg19: chr6-42848664;