X-101391265-G-A

Variant names:

• chrX-101391265-G-A
• rs1927788614
• ENST00000465744.5:n.152G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_021029.6(RPL36A):​c.4-194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 478,547 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000021 (0 hom. 1 hem.)
• Consequence: RPL36A NM_021029.6 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.493
• Publications: 0 publications found

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:48349): (RPL36A-HNRNPH2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ribosomal protein L36a and heterogeneous nuclear ribonucleoprotein H2 (H') genes on chromosome X. The read-through transcript produces a protein with similarity to the protein encoded by the upstream locus, ribosomal protein L36a. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant X-101391265-G-A is Benign according to our data. Variant chrX-101391265-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050211.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL36A	NM_021029.6	c.4-194G>A		intron_variant	Intron 1 of 4	ENST00000553110.8	NP_066357.3
RPL36A-HNRNPH2	NM_001199973.2	c.4-194G>A		intron_variant	Intron 1 of 4		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.4-194G>A		intron_variant	Intron 1 of 3		NP_001186903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL36A	ENST00000553110.8	c.4-194G>A		intron_variant	Intron 1 of 4	1	NM_021029.6	ENSP00000446503.2
RPL36A-HNRNPH2	ENST00000409170.3	c.4-194G>A		intron_variant	Intron 1 of 4	4		ENSP00000386655.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000209 AC: 1 AN: 478547 Hom.: 0 Cov.: 7 AF XY: 0.00000709 AC XY: 1 AN XY: 140955

African (AFR) AF: 0.00 AC: 0 AN: 13076

American (AMR) AF: 0.00 AC: 0 AN: 19036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11420

East Asian (EAS) AF: 0.00 AC: 0 AN: 26003

South Asian (SAS) AF: 0.00 AC: 0 AN: 32206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35065

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1709

European-Non Finnish (NFE) AF: 0.00000317 AC: 1 AN: 315315

Other (OTH) AF: 0.00 AC: 0 AN: 24717

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLA-related disorder Benign:1

Nov 09, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.71
CADD	Benign	7.8
DANN	Benign	0.78
PhyloP100		0.49
PromoterAI		-0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1927788614; hg19: chrX-100646253;