chrX-101391167-A-G

Variant names:

• chrX-101391167-A-G
• rs782691804
• ENST00000465744.5:n.54A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_021029.6(RPL36A):​c.3+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 842,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 63 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: 𝑓 0.0011 (0 hom., 43 hem., cov: 23)
  • Exomes 𝑓: 0.00013 (0 hom. 20 hem.)
• Consequence: RPL36A NM_021029.6 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.60
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-101391167-A-G is Benign according to our data. Variant chrX-101391167-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3048977.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL36A	NM_021029.6	c.3+121A>G		intron_variant	Intron 1 of 4	ENST00000553110.8	NP_066357.3
RPL36A-HNRNPH2	NM_001199973.2	c.3+121A>G		intron_variant	Intron 1 of 4		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.3+121A>G		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.3+121A>G		intron_variant	Intron 1 of 4	1	NM_021029.6	ENSP00000446503.2
RPL36A-HNRNPH2	ENST00000409170.3	c.3+121A>G		intron_variant	Intron 1 of 4	4		ENSP00000386655.4

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 118 AN: 112314 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000376

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 95 AN: 729962 Hom.: 0 Cov.: 12 AF XY: 0.000105 AC XY: 20 AN XY: 190680

African (AFR) AF: 0.00394 AC: 74 AN: 18798

American (AMR) AF: 0.0000331 AC: 1 AN: 30212

Ashkenazi Jewish (ASJ) AF: 0.0000678 AC: 1 AN: 14759

East Asian (EAS) AF: 0.000141 AC: 4 AN: 28294

South Asian (SAS) AF: 0.0000244 AC: 1 AN: 41016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38481

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3272

European-Non Finnish (NFE) AF: 0.0000173 AC: 9 AN: 521646

Other (OTH) AF: 0.000149 AC: 5 AN: 33484

GnomAD4 genome AF: 0.00105 AC: 118 AN: 112368 Hom.: 0 Cov.: 23 AF XY: 0.00124 AC XY: 43 AN XY: 34540

African (AFR) AF: 0.00368 AC: 114 AN: 30979

American (AMR) AF: 0.000376 AC: 4 AN: 10639

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.00 AC: 0 AN: 2728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53218

Other (OTH) AF: 0.00 AC: 0 AN: 1521

Alfa AF: 0.000854 Hom.: 2

Bravo AF: 0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLA-related disorder Benign:1

Apr 04, 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	-0.80
CADD	Benign	0.015
DANN	Benign	0.48
PhyloP100		-4.6
PromoterAI		0.019	Neutral
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: rs782691804; hg19: chrX-100646155;