chr5-172968481-G-C

Variant names:

• chr5-172968481-G-C
• rs1179448621
• NM_016093.4:c.191G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016093.4(RPL26L1):​c.191G>C​(p.Gly64Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G64V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPL26L1 NM_016093.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.57
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

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.191G>C	p.Gly64Ala	missense	Exon 3 of 4	NP_057177.1	Q9UNX3
	RPL26L1	NM_001317980.2		c.191G>C	p.Gly64Ala	missense	Exon 3 of 4	NP_001304909.1	Q9UNX3
	RPL26L1	NM_001317981.2		c.191G>C	p.Gly64Ala	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.191G>C	p.Gly64Ala	missense	Exon 3 of 4	ENSP00000265100.2	Q9UNX3
	RPL26L1	ENST00000519156.1	TSL:1	c.191G>C	p.Gly64Ala	missense	Exon 2 of 3	ENSP00000430673.1	E5RIT6
	RPL26L1	ENST00000519239.5	TSL:2	c.191G>C	p.Gly64Ala	missense	Exon 3 of 4	ENSP00000430147.1	Q9UNX3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		9.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.050	T
Polyphen		0.98	D
Vest4		0.76
MutPred		0.76		Loss of stability (P = 0.0541)
MVP		0.78
MPC		1.4
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.57
gMVP		0.64
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs1179448621; hg19: chr5-172395484;