6-42884659-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.358C>T(p.Arg120Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,613,712 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: RPL7L1 NM_001366481.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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=0.34079564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL7L1	NM_001366481.3	c.358C>T	p.Arg120Cys	missense_variant	4/6	ENST00000493763.7
RPL7L1	NM_198486.5	c.358C>T	p.Arg120Cys	missense_variant	4/7
RPL7L1	NR_134562.3	n.769C>T		non_coding_transcript_exon_variant	4/7
RPL7L1	NR_134563.3	n.547C>T		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL7L1	ENST00000493763.7	c.358C>T	p.Arg120Cys	missense_variant	4/6	1	NM_001366481.3	P1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000131 AC: 33 AN: 251372 Hom.: 1 AF XY: 0.000140 AC XY: 19 AN XY: 135884

Gnomad AFR exome AF: 0.000123

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: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000261 AC: 381 AN: 1461450 Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 166 AN XY: 727052

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000320

Gnomad4 OTH exome AF: 0.000364

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74446

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000176 Hom.: 0

Bravo AF: 0.000185

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000218

EpiControl AF: 0.000474

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 16, 2021

The c.331C>T (p.R111C) alteration is located in exon 4 (coding exon 4) of the RPL7L1 gene. This alteration results from a C to T substitution at nucleotide position 331, causing the arginine (R) at amino acid position 111 to be replaced by a cysteine (C). 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	0.29
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Uncertain	-0.020
Cadd	Pathogenic	28
Dann	Uncertain	1.0
Eigen	Benign	-0.013
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.77	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
REVEL	Pathogenic	0.68
MVP		0.53
MPC		0.53
ClinPred		0.17	T
GERP RS		4.3
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199719364; hg19: chr6-42852397; COSMIC: COSV59034828; COSMIC: COSV59034828;