X-101391786-C-T

Variant names:

• chrX-101391786-C-T
• rs3027595
• NM_021029.6:c.141C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BP7 BS2

The NM_021029.6(RPL36A):​c.141C>T​(p.Gly47Gly) 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. 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, multiple submitters, no conflicts B:2
• 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: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 -13 ACMG points.

• 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL36A	NM_021029.6	c.141C>T	p.Gly47Gly	synonymous_variant	Exon 3 of 5	ENST00000553110.8	NP_066357.3
RPL36A-HNRNPH2	NM_001199973.2	c.141C>T	p.Gly47Gly	synonymous_variant	Exon 3 of 5		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.141C>T	p.Gly47Gly	synonymous_variant	Exon 3 of 4		NP_001186903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL36A	ENST00000553110.8	c.141C>T	p.Gly47Gly	synonymous_variant	Exon 3 of 5	1	NM_021029.6	ENSP00000446503.2
RPL36A-HNRNPH2	ENST00000409170.3	c.141C>T	p.Gly47Gly	synonymous_variant	Exon 3 of 5	4		ENSP00000386655.4

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 470 AN: 111760 Hom.: 2 Cov.: 22

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

GnomAD2 exomes AF: 0.00407 AC: 738 AN: 181291 AF XY: 0.00393

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 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 AC: 17 AN: 26324

Gnomad4 AMR exome AF: 0.00129 AC: 45 AN: 34870

Gnomad4 ASJ exome AF: 0.00192 AC: 37 AN: 19309

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30199

Gnomad4 SAS exome AF: 0.00201 AC: 108 AN: 53682

Gnomad4 FIN exome AF: 0.00385 AC: 156 AN: 40519

Gnomad4 NFE exome AF: 0.00783 AC: 6591 AN: 841800

Gnomad4 Remaining exome AF: 0.00528 AC: 243 AN: 46055

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 AC: 0.000876766 AN: 0.000876766

Gnomad4 AMR AF: 0.00515 AC: 0.00515021 AN: 0.00515021

Gnomad4 ASJ AF: 0.00188 AC: 0.00188466 AN: 0.00188466

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00111 AC: 0.001114 AN: 0.001114

Gnomad4 FIN AF: 0.00283 AC: 0.00282533 AN: 0.00282533

Gnomad4 NFE AF: 0.00675 AC: 0.00674939 AN: 0.00674939

Gnomad4 OTH AF: 0.00327 AC: 0.00327225 AN: 0.00327225

Alfa AF: 0.00486 Hom.: 41

Bravo AF: 0.00430

EpiCase AF: 0.00551

EpiControl AF: 0.00854

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.93
Mutation Taster		=298/2	polymorphism (auto)

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;