5-172969464-C-T

Variant names:

• chr5-172969464-C-T
• rs545379858
• NM_016093.4:c.361C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016093.4(RPL26L1):​c.361C>T​(p.Arg121Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: RPL26L1 NM_016093.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 8 AD gene.

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.361C>T	p.Arg121Cys	missense	Exon 4 of 4	NP_057177.1	Q9UNX3
	RPL26L1	NM_001317980.2		c.361C>T	p.Arg121Cys	missense	Exon 4 of 4	NP_001304909.1	Q9UNX3
	RPL26L1	NM_001317981.2		c.361C>T	p.Arg121Cys	missense	Exon 4 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.361C>T	p.Arg121Cys	missense	Exon 4 of 4	ENSP00000265100.2	Q9UNX3
	RPL26L1	ENST00000519156.1	TSL:1	c.361C>T	p.Arg121Cys	missense	Exon 3 of 3	ENSP00000430673.1	E5RIT6
	RPL26L1	ENST00000519239.5	TSL:2	c.361C>T	p.Arg121Cys	missense	Exon 4 of 4	ENSP00000430147.1	Q9UNX3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152116 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251136 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000108 AC: 158 AN: 1461396 Hom.: 0 Cov.: 32 AF XY: 0.000103 AC XY: 75 AN XY: 727028

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000179 AC: 6 AN: 33462

American (AMR) AF: 0.0000671 AC: 3 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1111680

Other (OTH) AF: 0.000232 AC: 14 AN: 60360

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74416

African (AFR) AF: 0.0000241 AC: 1 AN: 41534

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.53		Loss of sheet (P = 0.0011)
MVP		0.46
MPC		0.96
ClinPred		0.90	D
GERP RS		4.6
Varity_R		0.82
gMVP		0.45
Mutation Taster		=73/27	polymorphism

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: rs545379858; hg19: chr5-172396467;