2-101004153-C-T

Variant names:

• chr2-101004153-C-T
• rs777298130
• NM_000993.5:c.108-5C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000993.5(RPL31):​c.108-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RPL31 NM_000993.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004338
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.523
• Publications: 0 publications found

Genes affected

RPL31 (HGNC:10334): (ribosomal protein L31) Ribosomes, the 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 belongs to the L31E family of ribosomal proteins. It is located in the cytoplasm. Higher levels of expression of this gene in familial adenomatous polyps compared to matched normal tissues have been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPL31 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-101004153-C-T is Benign according to our data. Variant chr2-101004153-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2786194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000993.5. 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
	RPL31	NM_000993.5	MANE Select	c.108-5C>T		splice_region intron	N/A	NP_000984.1	P62899-1
	RPL31	NM_001098577.3		c.108-5C>T		splice_region intron	N/A	NP_001092047.1	P62899-2
	RPL31	NM_001099693.2		c.108-5C>T		splice_region intron	N/A	NP_001093163.1	P62899-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL31	ENST00000264258.8	TSL:1 MANE Select	c.108-5C>T		splice_region intron	N/A	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.108-5C>T		splice_region intron	N/A	ENSP00000386681.1	P62899-1
	RPL31	ENST00000409320.7	TSL:1	c.108-5C>T		splice_region intron	N/A	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250046 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460654 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726604

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.0000225 AC: 1 AN: 44470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111534

Other (OTH) AF: 0.0000166 AC: 1 AN: 60340

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.0
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: rs777298130; hg19: chr2-101620615;