NM_000982.4:c.130-69G>A

Variant names:

• chr13-27255173-G-A
• rs3094293
• NM_000982.4:c.130-69G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000982.4(RPL21):​c.130-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 793,018 control chromosomes in the GnomAD database, including 392,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73812 hom., cov: 32)
  • Exomes 𝑓: 1.0 (318987 hom.)
• Consequence: RPL21 NM_000982.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.38
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-27255173-G-A is Benign according to our data. Variant chr13-27255173-G-A is described in ClinVar as [Benign]. Clinvar id is 1235163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4	c.130-69G>A		intron_variant	Intron 3 of 5	ENST00000311549.11	NP_000973.2
SNORA27	NR_002575.1	n.-228G>A		upstream_gene_variant
SNORD102	NR_002574.1	n.*38G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11	c.130-69G>A		intron_variant	Intron 3 of 5	1	NM_000982.4	ENSP00000346027.4

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149818 AN: 152236 Hom.: 73760 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.990

GnomAD2 exomes AF: 0.996 AC: 248309 AN: 249356 AF XY: 0.997

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.998

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.998 AC: 639285 AN: 640664 Hom.: 318987 Cov.: 7 AF XY: 0.998 AC XY: 347836 AN XY: 348424

African (AFR) AF: 0.946 AC: 16916 AN: 17886

American (AMR) AF: 0.997 AC: 43574 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 20974 AN: 21014

East Asian (EAS) AF: 1.00 AC: 36068 AN: 36068

South Asian (SAS) AF: 1.00 AC: 70002 AN: 70012

European-Finnish (FIN) AF: 1.00 AC: 52994 AN: 52994

Middle Eastern (MID) AF: 0.997 AC: 4163 AN: 4174

European-Non Finnish (NFE) AF: 1.00 AC: 361261 AN: 361334

Other (OTH) AF: 0.995 AC: 33333 AN: 33484

GnomAD4 genome AF: 0.984 AC: 149928 AN: 152354 Hom.: 73812 Cov.: 32 AF XY: 0.985 AC XY: 73361 AN XY: 74502

African (AFR) AF: 0.946 AC: 39308 AN: 41570

American (AMR) AF: 0.992 AC: 15184 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4833 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68031 AN: 68048

Other (OTH) AF: 0.990 AC: 2095 AN: 2116

Alfa AF: 0.994 Hom.: 90920

Bravo AF: 0.982

Asia WGS AF: 0.998 AC: 3470 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.23
PhyloP100		-5.4
Mutation Taster		=100/0	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: rs3094293; hg19: chr13-27829310;