NM_000982.4:c.394-11dupT

Variant names:

• chr13-27256416-C-CT
• rs749953441
• NM_000982.4:c.394-11dupT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000982.4(RPL21):​c.394-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,546,062 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: RPL21 NM_000982.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21
• Publications: 0 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 -6 ACMG points.

• BP6: Variant 13-27256416-C-CT is Benign according to our data. Variant chr13-27256416-C-CT is described in ClinVar as Likely_benign. ClinVar VariationId is 1988640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 89 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000982.4. 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
	RPL21	NM_000982.4	MANE Select	c.394-11dupT		intron	N/A	NP_000973.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL21	ENST00000311549.11	TSL:1 MANE Select	c.394-20_394-19insT		intron	N/A	ENSP00000346027.4	P46778
	RPL21	ENST00000939435.1		c.454-20_454-19insT		intron	N/A	ENSP00000609494.1
	RPL21	ENST00000939430.1		c.412-20_412-19insT		intron	N/A	ENSP00000609489.1

Frequencies

GnomAD3 genomes AF: 0.000589 AC: 89 AN: 151222 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00204

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000354

Gnomad OTH AF: 0.00338

GnomAD2 exomes AF: 0.000996 AC: 220 AN: 220924 AF XY: 0.000972

Gnomad AFR exome AF: 0.000439

Gnomad AMR exome AF: 0.00155

Gnomad ASJ exome AF: 0.00294

Gnomad EAS exome AF: 0.000247

Gnomad FIN exome AF: 0.0000508

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00114 AC: 1592 AN: 1394724 Hom.: 0 Cov.: 25 AF XY: 0.00112 AC XY: 783 AN XY: 697172

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

African (AFR) AF: 0.000688 AC: 22 AN: 31976

American (AMR) AF: 0.00120 AC: 53 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.00278 AC: 71 AN: 25574

East Asian (EAS) AF: 0.000282 AC: 11 AN: 38968

South Asian (SAS) AF: 0.000840 AC: 71 AN: 84534

European-Finnish (FIN) AF: 0.000114 AC: 6 AN: 52842

Middle Eastern (MID) AF: 0.0110 AC: 62 AN: 5648

European-Non Finnish (NFE) AF: 0.00113 AC: 1189 AN: 1052924

Other (OTH) AF: 0.00184 AC: 107 AN: 58010

⚠️ 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: 0.000588 AC: 89 AN: 151338 Hom.: 1 Cov.: 32 AF XY: 0.000528 AC XY: 39 AN XY: 73920

African (AFR) AF: 0.000267 AC: 11 AN: 41258

American (AMR) AF: 0.00204 AC: 31 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000629 AC: 3 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10412

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000354 AC: 24 AN: 67786

Other (OTH) AF: 0.00334 AC: 7 AN: 2094

Alfa AF: 0.000651 Hom.: 0

Bravo AF: 0.000574

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	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: rs749953441; hg19: chr13-27830553; COSMIC: COSV55389744; COSMIC: COSV55389744;