chrX-101391195-C-T

Variant names:

• chrX-101391195-C-T
• rs187269060
• NM_021029.6:c.3+149C>T

Variant summary

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

The NM_001199973.2(RPL36A-HNRNPH2):​c.3+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 691,333 control chromosomes in the GnomAD database, including 1 homozygotes. There are 84 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 0.0016 (0 hom., 54 hem., cov: 23)
  • Exomes 𝑓: 0.00021 (1 hom. 30 hem.)
• Consequence: RPL36A-HNRNPH2 NM_001199973.2 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.33
• 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=-0.72).
• BP6: Variant X-101391195-C-T is Benign according to our data. Variant chrX-101391195-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3040732.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 54 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL36A	NM_021029.6	MANE Select	c.3+149C>T		intron	N/A	NP_066357.3
	RPL36A-HNRNPH2	NM_001199973.2		c.3+149C>T		intron	N/A	NP_001186902.2
	RPL36A-HNRNPH2	NM_001199974.2		c.3+149C>T		intron	N/A	NP_001186903.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL36A	ENST00000553110.8	TSL:1 MANE Select	c.3+149C>T		intron	N/A	ENSP00000446503.2
	RPL36A	ENST00000427805.6	TSL:1	c.111+149C>T		intron	N/A	ENSP00000404375.2
	RPL36A	ENST00000614077.4	TSL:1	c.111+149C>T		intron	N/A	ENSP00000483017.1

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 176 AN: 112225 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000283

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000366

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00134

GnomAD4 exome AF: 0.000211 AC: 122 AN: 579057 Hom.: 1 Cov.: 9 AF XY: 0.000194 AC XY: 30 AN XY: 154901

African (AFR) AF: 0.00500 AC: 77 AN: 15386

American (AMR) AF: 0.000553 AC: 13 AN: 23521

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12525

East Asian (EAS) AF: 0.00 AC: 0 AN: 27342

South Asian (SAS) AF: 0.0000853 AC: 3 AN: 35157

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36290

Middle Eastern (MID) AF: 0.00174 AC: 5 AN: 2867

European-Non Finnish (NFE) AF: 0.00000754 AC: 3 AN: 397719

Other (OTH) AF: 0.000743 AC: 21 AN: 28250

GnomAD4 genome AF: 0.00160 AC: 180 AN: 112276 Hom.: 0 Cov.: 23 AF XY: 0.00157 AC XY: 54 AN XY: 34438

African (AFR) AF: 0.00562 AC: 174 AN: 30948

American (AMR) AF: 0.000283 AC: 3 AN: 10618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3537

South Asian (SAS) AF: 0.000367 AC: 1 AN: 2726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53230

Other (OTH) AF: 0.00132 AC: 2 AN: 1515

Alfa AF: 0.00171 Hom.: 4

Bravo AF: 0.00184

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GLA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.38
DANN	Benign	0.80
PhyloP100		-1.3
PromoterAI		-0.10	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: rs187269060; hg19: chrX-100646183;