X-101391216-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021029.6(RPL36A):c.3+170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000602 in 624,199 control chromosomes in the GnomAD database, including 1 homozygotes. There are 99 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., 68 hem., cov: 23)
  • Exomes 𝑓: 0.00028 (0 hom. 31 hem.)
• Consequence: RPL36A NM_021029.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

Genes affected

RPL36A (HGNC:10359): (ribosomal protein L36a) Cytoplasmic ribosomes, 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, which shares sequence similarity with yeast ribosomal protein L44, belongs to the L44E (L36AE) family of ribosomal proteins. Although this gene has been referred to as ribosomal protein L44 (RPL44), its official name is ribosomal protein L36a (RPL36A). This gene and the human gene officially named ribosomal protein L36a-like (RPL36AL) encode nearly identical proteins; however, they are distinct genes. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Naturally occurring read-through transcription occurs between this locus and the heterogeneous nuclear ribonucleoprotein H2 (H') gene. [provided by RefSeq, Jan 2011]

RPL36A-HNRNPH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant X-101391216-G-A is Benign according to our data. Variant chrX-101391216-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3031516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 68 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL36A	NM_021029.6	c.3+170G>A		intron_variant		ENST00000553110.8
RPL36A-HNRNPH2	NM_001199973.2	c.3+170G>A		intron_variant
RPL36A-HNRNPH2	NM_001199974.2	c.3+170G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL36A	ENST00000553110.8	c.3+170G>A		intron_variant		1	NM_021029.6	P1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 231 AN: 112382 Hom.: 1 Cov.: 23 AF XY: 0.00197 AC XY: 68 AN XY: 34534

Gnomad AFR AF: 0.00673

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000939

Gnomad OTH AF: 0.00134

GnomAD4 exome AF: 0.000283 AC: 145 AN: 511762 Hom.: 0 Cov.: 8 AF XY: 0.000217 AC XY: 31 AN XY: 143052

Gnomad4 AFR exome AF: 0.00753

Gnomad4 AMR exome AF: 0.000623

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000300

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000586

Gnomad4 OTH exome AF: 0.000808

GnomAD4 genome AF: 0.00205 AC: 231 AN: 112437 Hom.: 1 Cov.: 23 AF XY: 0.00197 AC XY: 68 AN XY: 34599

Gnomad4 AFR AF: 0.00671

Gnomad4 AMR AF: 0.00141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000365

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000939

Gnomad4 OTH AF: 0.00132

Alfa AF: 0.00157 Hom.: 3

Bravo AF: 0.00254

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GLA-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	7.2
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs782144276; hg19: chrX-100646204;