ENST00000465744.5:n.103G>A

Variant names:

• chrX-101391216-G-A
• rs782144276
• ENST00000465744.5:n.103G>A

Variant summary

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

The ENST00000465744.5(RPL36A):​n.103G>A variant causes a non coding transcript exon 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., 68 hem., cov: 23)
  • Exomes 𝑓: 0.00028 (0 hom. 31 hem.)
• Consequence: RPL36A ENST00000465744.5 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.24
• 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=-0.7).
• 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 no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 68 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL36A	NM_021029.6	c.3+170G>A		intron_variant	Intron 1 of 4	ENST00000553110.8	NP_066357.3
RPL36A-HNRNPH2	NM_001199973.2	c.3+170G>A		intron_variant	Intron 1 of 4		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.3+170G>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.3+170G>A		intron_variant	Intron 1 of 4	1	NM_021029.6	ENSP00000446503.2
RPL36A-HNRNPH2	ENST00000409170.3	c.3+170G>A		intron_variant	Intron 1 of 4	4		ENSP00000386655.4

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 231 AN: 112382 Hom.: 1 Cov.: 23

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

African (AFR) AF: 0.00753 AC: 105 AN: 13951

American (AMR) AF: 0.000623 AC: 13 AN: 20854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11744

East Asian (EAS) AF: 0.00 AC: 0 AN: 26648

South Asian (SAS) AF: 0.0000300 AC: 1 AN: 33279

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35213

Middle Eastern (MID) AF: 0.00116 AC: 3 AN: 2590

European-Non Finnish (NFE) AF: 0.00000586 AC: 2 AN: 341502

Other (OTH) AF: 0.000808 AC: 21 AN: 25981

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

African (AFR) AF: 0.00671 AC: 208 AN: 30996

American (AMR) AF: 0.00141 AC: 15 AN: 10667

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.000365 AC: 1 AN: 2740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6177

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

European-Non Finnish (NFE) AF: 0.0000939 AC: 5 AN: 53239

Other (OTH) AF: 0.00132 AC: 2 AN: 1516

Alfa AF: 0.00157 Hom.: 3

Bravo AF: 0.00254

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLA-related disorder Benign:1

Apr 03, 2023

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	-0.70
CADD	Benign	7.2
DANN	Benign	0.86
PhyloP100		1.2
PromoterAI		-0.053	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: rs782144276; hg19: chrX-100646204;