X-101391786-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_021029.6(RPL36A):c.141C>T(p.Gly47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00635 in 1,208,700 control chromosomes in the GnomAD database, including 18 homozygotes. There are 2,493 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., 141 hem., cov: 22)
  • Exomes 𝑓: 0.0066 (16 hom. 2352 hem.)
• Consequence: RPL36A NM_021029.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-101391786-C-T is Benign according to our data. Variant chrX-101391786-C-T is described in ClinVar as [Benign]. Clinvar id is 708163.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-101391786-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL36A	NM_021029.6	c.141C>T	p.Gly47=	synonymous_variant	3/5	ENST00000553110.8
RPL36A-HNRNPH2	NM_001199973.2	c.141C>T	p.Gly47=	synonymous_variant	3/5
RPL36A-HNRNPH2	NM_001199974.2	c.141C>T	p.Gly47=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL36A	ENST00000553110.8	c.141C>T	p.Gly47=	synonymous_variant	3/5	1	NM_021029.6	P1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 470 AN: 111760 Hom.: 2 Cov.: 22 AF XY: 0.00416 AC XY: 141 AN XY: 33916

Gnomad AFR AF: 0.000879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00516

Gnomad ASJ AF: 0.00188

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00675

Gnomad OTH AF: 0.00332

GnomAD3 exomes AF: 0.00407 AC: 738 AN: 181291 Hom.: 2 AF XY: 0.00393 AC XY: 259 AN XY: 65843

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.00136

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00179

Gnomad FIN exome AF: 0.00313

Gnomad NFE exome AF: 0.00733

Gnomad OTH exome AF: 0.00334

GnomAD4 exome AF: 0.00657 AC: 7204 AN: 1096883 Hom.: 16 Cov.: 31 AF XY: 0.00649 AC XY: 2352 AN XY: 362297

Gnomad4 AFR exome AF: 0.000646

Gnomad4 AMR exome AF: 0.00129

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00201

Gnomad4 FIN exome AF: 0.00385

Gnomad4 NFE exome AF: 0.00783

Gnomad4 OTH exome AF: 0.00528

GnomAD4 genome AF: 0.00420 AC: 470 AN: 111817 Hom.: 2 Cov.: 22 AF XY: 0.00415 AC XY: 141 AN XY: 33983

Gnomad4 AFR AF: 0.000877

Gnomad4 AMR AF: 0.00515

Gnomad4 ASJ AF: 0.00188

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00111

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00675

Gnomad4 OTH AF: 0.00327

Alfa AF: 0.00486 Hom.: 41

Bravo AF: 0.00430

EpiCase AF: 0.00551

EpiControl AF: 0.00854

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	11
Dann	Benign	0.93

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: rs3027595; hg19: chrX-100646774;