chr17-8377650-T-C

Variant names:

• chr17-8377650-T-C
• rs1325509343
• NM_000987.5:c.352A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000987.5(RPL26):​c.352A>G​(p.Ile118Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPL26 NM_000987.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16

Genes affected

RPL26 (HGNC:10327): (ribosomal protein L26) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L24P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ENSG00000263809 (HGNC:):

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=0.27624884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL26	NM_000987.5	c.352A>G	p.Ile118Val	missense_variant	Exon 4 of 4	ENST00000648839.1	NP_000978.1
RPL26	NM_001315530.2	c.352A>G	p.Ile118Val	missense_variant	Exon 4 of 4		NP_001302459.1
RPL26	NM_001315531.2	c.352A>G	p.Ile118Val	missense_variant	Exon 4 of 4		NP_001302460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL26	ENST00000648839.1	c.352A>G	p.Ile118Val	missense_variant	Exon 4 of 4		NM_000987.5	ENSP00000498177.1
ENSG00000263809	ENST00000582471.1	n.310-1546A>G		intron_variant	Intron 3 of 5	5		ENSP00000463847.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249288 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134928

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459872 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T;T;T;T;T
Eigen	Benign	0.080
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	.;.;.;.;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.92	.;N;.;.;.
REVEL	Benign	0.20
Sift	Uncertain	0.021	.;D;.;.;.
Sift4G	Uncertain	0.059	.;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.34, 0.34, 0.33
MutPred		0.51		Loss of methylation at K122 (P = 0.1073);Loss of methylation at K122 (P = 0.1073);Loss of methylation at K122 (P = 0.1073);Loss of methylation at K122 (P = 0.1073);Loss of methylation at K122 (P = 0.1073);
MVP		0.41
MPC		0.84
ClinPred		0.54	D
GERP RS		4.4
Varity_R		0.19
gMVP		0.35

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: rs1325509343; hg19: chr17-8280968;