chr13-27255271-C-T

Variant names:

• chr13-27255271-C-T
• rs61738475
• NM_000982.4:c.159C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000982.4(RPL21):​c.159C>T​(p.Pro53Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,446,834 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (41 hom.)
• Consequence: RPL21 NM_000982.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0560
• Publications: 2 publications found

Genes affected

RPL21 (HGNC:10313): (ribosomal protein L21) 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 L21E 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. [provided by RefSeq, Jul 2008]

SNORA27 (HGNC:32617): (small nucleolar RNA, H/ACA box 27)

SNORD102 (HGNC:10099): (small nucleolar RNA, C/D box 102)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 13-27255271-C-T is Benign according to our data. Variant chr13-27255271-C-T is described in ClinVar as [Benign]. Clinvar id is 1271809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.056 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4	c.159C>T	p.Pro53Pro	synonymous_variant	Exon 4 of 6	ENST00000311549.11	NP_000973.2
SNORA27	NR_002575.1	n.-130C>T		upstream_gene_variant
SNORD102	NR_002574.1	n.*136C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11	c.159C>T	p.Pro53Pro	synonymous_variant	Exon 4 of 6	1	NM_000982.4	ENSP00000346027.4

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2375 AN: 152114 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00411 AC: 1032 AN: 251366 AF XY: 0.00280

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00156 AC: 2021 AN: 1294602 Hom.: 41 Cov.: 20 AF XY: 0.00132 AC XY: 865 AN XY: 653160

African (AFR) AF: 0.0529 AC: 1582 AN: 29884

American (AMR) AF: 0.00380 AC: 169 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25124

East Asian (EAS) AF: 0.00 AC: 0 AN: 38944

South Asian (SAS) AF: 0.000217 AC: 18 AN: 82974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00257 AC: 14 AN: 5458

European-Non Finnish (NFE) AF: 0.0000146 AC: 14 AN: 959496

Other (OTH) AF: 0.00408 AC: 224 AN: 54876

GnomAD4 genome AF: 0.0157 AC: 2384 AN: 152232 Hom.: 67 Cov.: 32 AF XY: 0.0150 AC XY: 1120 AN XY: 74446

African (AFR) AF: 0.0537 AC: 2231 AN: 41516

American (AMR) AF: 0.00726 AC: 111 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68022

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00880 Hom.: 19

Bravo AF: 0.0182

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.4
DANN	Benign	0.69
PhyloP100		0.056
Mutation Taster		=94/6	polymorphism (auto)

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: rs61738475; hg19: chr13-27829408;