NM_000993.5:c.252C>T

Variant names:

• chr2-101005977-C-T
• rs138783248
• NM_000993.5:c.252C>T

Variant summary

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

The NM_000993.5(RPL31):​c.252C>T​(p.Ile84Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,612,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: RPL31 NM_000993.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.25
• Publications: 1 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]

TBC1D8 (HGNC:17791): (TBC1 domain family member 8) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP6: Variant 2-101005977-C-T is Benign according to our data. Variant chr2-101005977-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 787582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.25 with no splicing effect.
• BS2: High AC in GnomAd4 at 114 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.252C>T	p.Ile84Ile	synonymous	Exon 4 of 5	NP_000984.1	P62899-1
	RPL31	NM_001098577.3		c.252C>T	p.Ile84Ile	synonymous	Exon 4 of 5	NP_001092047.1	P62899-2
	RPL31	NM_001099693.2		c.252C>T	p.Ile84Ile	synonymous	Exon 4 of 4	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.252C>T	p.Ile84Ile	synonymous	Exon 4 of 5	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.252C>T	p.Ile84Ile	synonymous	Exon 3 of 4	ENSP00000386681.1	P62899-1
	RPL31	ENST00000409320.7	TSL:1	c.252C>T	p.Ile84Ile	synonymous	Exon 4 of 4	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000626 AC: 157 AN: 250756 AF XY: 0.000612

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.00109 AC: 1599 AN: 1460358 Hom.: 0 Cov.: 31 AF XY: 0.00109 AC XY: 795 AN XY: 726492

African (AFR) AF: 0.000150 AC: 5 AN: 33436

American (AMR) AF: 0.000292 AC: 13 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86066

European-Finnish (FIN) AF: 0.000375 AC: 20 AN: 53390

Middle Eastern (MID) AF: 0.00204 AC: 10 AN: 4908

European-Non Finnish (NFE) AF: 0.00134 AC: 1490 AN: 1111844

Other (OTH) AF: 0.000978 AC: 59 AN: 60306

GnomAD4 genome AF: 0.000749 AC: 114 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74422

African (AFR) AF: 0.000337 AC: 14 AN: 41534

American (AMR) AF: 0.000654 AC: 10 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.000759

EpiCase AF: 0.00169

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		1.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=98/2	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: rs138783248; hg19: chr2-101622439; COSMIC: COSV51823255; COSMIC: COSV51823255;