NM_000982.4:c.-12-91C>A

Variant names:

• chr13-27253674-C-A
• rs3094292
• NM_000982.4:c.-12-91C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000982.4(RPL21):​c.-12-91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 597,270 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: 34)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: RPL21 NM_000982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 3 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]

RPL21 Gene-Disease associations (from GenCC):

• hypotrichosis 12

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4	c.-12-91C>A		intron_variant	Intron 1 of 5	ENST00000311549.11	NP_000973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11	c.-12-91C>A		intron_variant	Intron 1 of 5	1	NM_000982.4	ENSP00000346027.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000167 AC: 1 AN: 597270 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 323578

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

African (AFR) AF: 0.00 AC: 0 AN: 16370

American (AMR) AF: 0.00 AC: 0 AN: 38804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20112

East Asian (EAS) AF: 0.00 AC: 0 AN: 33678

South Asian (SAS) AF: 0.00 AC: 0 AN: 66232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2472

European-Non Finnish (NFE) AF: 0.00000295 AC: 1 AN: 338788

Other (OTH) AF: 0.00 AC: 0 AN: 31396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.75
PhyloP100		0.089
PromoterAI		-0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3094292; hg19: chr13-27827811;