5-172969489-G-T

Position:

• chr5-172969489-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016093.4(RPL26L1):​c.386G>T​(p.Gly129Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL26L1 NM_016093.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

Genes affected

RPL26L1 (HGNC:17050): (ribosomal protein L26 like 1) This gene encodes a protein that shares high sequence similarity with ribosomal protein L26. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24181539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL26L1	NM_016093.4	c.386G>T	p.Gly129Val	missense_variant	4/4	ENST00000265100.6	NP_057177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL26L1	ENST00000265100.6	c.386G>T	p.Gly129Val	missense_variant	4/4	1	NM_016093.4	ENSP00000265100.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000479 AC: 7 AN: 1461418 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727010

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: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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

Jun 18, 2021

The c.386G>T (p.G129V) alteration is located in exon 4 (coding exon 3) of the RPL26L1 gene. This alteration results from a G to T substitution at nucleotide position 386, causing the glycine (G) at amino acid position 129 to be replaced by a valine (V). 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	0.30
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T;T;T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	.;.;.;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M;M;M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Benign	0.068	T;T;T;T
Polyphen		0.11	B;B;B;B
Vest4		0.50
MutPred		0.36		Gain of methylation at K130 (P = 0.05);Gain of methylation at K130 (P = 0.05);Gain of methylation at K130 (P = 0.05);Gain of methylation at K130 (P = 0.05);
MVP		0.44
MPC		0.96
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.26
gMVP		0.28

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: rs1327598549; hg19: chr5-172396492;