rs72976842

Variant names:

• chr2-101005769-C-T
• rs72976842
• NM_000993.5:c.234-190C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000993.5(RPL31):​c.234-190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 596,016 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (469 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (127 hom.)
• Consequence: RPL31 NM_000993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0340
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-101005769-C-T is Benign according to our data. Variant chr2-101005769-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

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.234-190C>T		intron	N/A	NP_000984.1	P62899-1
	RPL31	NM_001098577.3		c.234-190C>T		intron	N/A	NP_001092047.1	P62899-2
	RPL31	NM_001099693.2		c.234-190C>T		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.234-190C>T		intron	N/A	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.234-190C>T		intron	N/A	ENSP00000386681.1	P62899-1
	RPL31	ENST00000409320.7	TSL:1	c.234-190C>T		intron	N/A	ENSP00000387163.3	P62899-3

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6321 AN: 152064 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0339

GnomAD4 exome AF: 0.00553 AC: 2455 AN: 443834 Hom.: 127 Cov.: 5 AF XY: 0.00467 AC XY: 1100 AN XY: 235546

African (AFR) AF: 0.143 AC: 1712 AN: 11950

American (AMR) AF: 0.0134 AC: 197 AN: 14654

Ashkenazi Jewish (ASJ) AF: 0.00188 AC: 26 AN: 13862

East Asian (EAS) AF: 0.00 AC: 0 AN: 29830

South Asian (SAS) AF: 0.000511 AC: 22 AN: 43020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30598

Middle Eastern (MID) AF: 0.00752 AC: 15 AN: 1994

European-Non Finnish (NFE) AF: 0.000540 AC: 147 AN: 272300

Other (OTH) AF: 0.0131 AC: 336 AN: 25626

GnomAD4 genome AF: 0.0417 AC: 6340 AN: 152182 Hom.: 469 Cov.: 32 AF XY: 0.0405 AC XY: 3015 AN XY: 74404

African (AFR) AF: 0.142 AC: 5887 AN: 41474

American (AMR) AF: 0.0214 AC: 327 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68024

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.0553 Hom.: 316

Bravo AF: 0.0487

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.72
PhyloP100		0.034
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs72976842; hg19: chr2-101622231;