5-172968463-T-G

Variant names:

• chr5-172968463-T-G
• rs1286968290
• NM_016093.4:c.173T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016093.4(RPL26L1):​c.173T>G​(p.Val58Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V58D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RPL26L1 NM_016093.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL26L1	NM_016093.4	MANE Select	c.173T>G	p.Val58Gly	missense	Exon 3 of 4	NP_057177.1	Q9UNX3
	RPL26L1	NM_001317980.2		c.173T>G	p.Val58Gly	missense	Exon 3 of 4	NP_001304909.1	Q9UNX3
	RPL26L1	NM_001317981.2		c.173T>G	p.Val58Gly	missense	Exon 3 of 4	NP_001304910.1	Q9UNX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL26L1	ENST00000265100.6	TSL:1 MANE Select	c.173T>G	p.Val58Gly	missense	Exon 3 of 4	ENSP00000265100.2	Q9UNX3
	RPL26L1	ENST00000519156.1	TSL:1	c.173T>G	p.Val58Gly	missense	Exon 2 of 3	ENSP00000430673.1	E5RIT6
	RPL26L1	ENST00000519239.5	TSL:2	c.173T>G	p.Val58Gly	missense	Exon 3 of 4	ENSP00000430147.1	Q9UNX3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461460 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727060

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		5.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.30	B
Vest4		0.75
MutPred		0.47		Loss of stability (P = 0.0115)
MVP		0.62
MPC		0.96
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.93
gMVP		0.75
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1286968290; hg19: chr5-172395466;