Variant chr6-42880926-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.23

Variant links:

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]

RPL7L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03445065).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPL7L1	NM_001366481.3 linkuse as main transcript	c.107A>G	p.Lys36Arg	missense_variant	2/6	ENST00000493763.7
RPL7L1	NM_198486.5 linkuse as main transcript	c.107A>G	p.Lys36Arg	missense_variant	2/7
RPL7L1	NR_134562.3 linkuse as main transcript	n.402A>G		non_coding_transcript_exon_variant	2/7
RPL7L1	NR_134563.3 linkuse as main transcript	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 linkuse as main transcript	c.107A>G	p.Lys36Arg	missense_variant	2/6	1	NM_001366481.3	P1	Q6DKI1-1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000989

AC XY:

134

AN XY:

135518

show subpopulations

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.:

Cov.:

AF XY:

0.000708

AC XY:

513

AN XY:

724220

show subpopulations

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:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74510

show subpopulations

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.:

Bravo

AF:

0.000529

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000733

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00160

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.059

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

REVEL

Benign

0.13

MVP

0.72

MPC

0.50

ClinPred

0.046

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over