13-27253674-C-T

Variant names:

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

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.-12-91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 749,288 control chromosomes in the GnomAD database, including 312,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59198 hom., cov: 34)
  • Exomes 𝑓: 0.92 (253206 hom.)
• Consequence: RPL21 NM_000982.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 13-27253674-C-T is Benign according to our data. Variant chr13-27253674-C-T is described in ClinVar as [Benign]. Clinvar id is 1243002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133693 AN: 152168 Hom.: 59163 Cov.: 34

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.920 AC: 549281 AN: 597002 Hom.: 253206 Cov.: 7 AF XY: 0.923 AC XY: 298659 AN XY: 323442

African (AFR) AF: 0.770 AC: 12599 AN: 16356

American (AMR) AF: 0.841 AC: 32612 AN: 38766

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 18385 AN: 20104

East Asian (EAS) AF: 0.942 AC: 31722 AN: 33676

South Asian (SAS) AF: 0.951 AC: 62979 AN: 66228

European-Finnish (FIN) AF: 0.931 AC: 45956 AN: 49378

Middle Eastern (MID) AF: 0.909 AC: 2243 AN: 2468

European-Non Finnish (NFE) AF: 0.928 AC: 314234 AN: 338650

Other (OTH) AF: 0.910 AC: 28551 AN: 31376

GnomAD4 genome AF: 0.879 AC: 133784 AN: 152286 Hom.: 59198 Cov.: 34 AF XY: 0.880 AC XY: 65544 AN XY: 74476

African (AFR) AF: 0.770 AC: 31991 AN: 41530

American (AMR) AF: 0.855 AC: 13070 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3470

East Asian (EAS) AF: 0.936 AC: 4853 AN: 5186

South Asian (SAS) AF: 0.954 AC: 4607 AN: 4830

European-Finnish (FIN) AF: 0.936 AC: 9941 AN: 10616

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63193 AN: 68040

Other (OTH) AF: 0.892 AC: 1885 AN: 2114

Alfa AF: 0.892 Hom.: 9181

Bravo AF: 0.865

Asia WGS AF: 0.922 AC: 3206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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	-0.87
CADD	Benign	4.8
DANN	Benign	0.77
PhyloP100		0.089
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3094292; hg19: chr13-27827811;