ENST00000409320.7:c.*175C>T

Variant names:

• chr2-101006266-C-T
• rs10934
• ENST00000409320.7:c.*175C>T

Variant summary

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

The ENST00000409320.7(RPL31):​c.*175C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,564,782 control chromosomes in the GnomAD database, including 71,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5466 hom., cov: 33)
  • Exomes 𝑓: 0.30 (65732 hom.)
• Consequence: RPL31 ENST00000409320.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.199
• Publications: 19 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 2-101006266-C-T is Benign according to our data. Variant chr2-101006266-C-T is described in ClinVar as Benign. ClinVar VariationId is 1234785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409320.7. 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.347-84C>T		intron	N/A	NP_000984.1	P62899-1
	RPL31	NM_001099693.2		c.*175C>T		3_prime_UTR	Exon 4 of 4	NP_001093163.1	P62899-3
	RPL31	NM_001098577.3		c.346+195C>T		intron	N/A	NP_001092047.1	P62899-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL31	ENST00000409320.7	TSL:1	c.*175C>T		3_prime_UTR	Exon 4 of 4	ENSP00000387163.3	P62899-3
	RPL31	ENST00000264258.8	TSL:1 MANE Select	c.347-84C>T		intron	N/A	ENSP00000264258.3	P62899-1
	RPL31	ENST00000409733.5	TSL:1	c.347-84C>T		intron	N/A	ENSP00000386681.1	P62899-1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38237 AN: 151920 Hom.: 5468 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.300 AC: 424160 AN: 1412744 Hom.: 65732 Cov.: 34 AF XY: 0.303 AC XY: 211771 AN XY: 698530

African (AFR) AF: 0.114 AC: 3603 AN: 31582

American (AMR) AF: 0.279 AC: 10077 AN: 36124

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 10440 AN: 23464

East Asian (EAS) AF: 0.168 AC: 6549 AN: 39084

South Asian (SAS) AF: 0.366 AC: 28407 AN: 77562

European-Finnish (FIN) AF: 0.262 AC: 13597 AN: 51842

Middle Eastern (MID) AF: 0.376 AC: 2100 AN: 5580

European-Non Finnish (NFE) AF: 0.305 AC: 332117 AN: 1089214

Other (OTH) AF: 0.296 AC: 17270 AN: 58292

GnomAD4 genome AF: 0.252 AC: 38239 AN: 152038 Hom.: 5466 Cov.: 33 AF XY: 0.252 AC XY: 18703 AN XY: 74308

African (AFR) AF: 0.118 AC: 4883 AN: 41478

American (AMR) AF: 0.286 AC: 4359 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1564 AN: 3468

East Asian (EAS) AF: 0.159 AC: 821 AN: 5166

South Asian (SAS) AF: 0.379 AC: 1823 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2811 AN: 10558

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20971 AN: 67976

Other (OTH) AF: 0.272 AC: 574 AN: 2112

Alfa AF: 0.295 Hom.: 28160

Bravo AF: 0.245

Asia WGS AF: 0.261 AC: 907 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	2.2
DANN	Benign	0.62
PhyloP100		0.20
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: rs10934; hg19: chr2-101622728; COSMIC: COSV51821389; COSMIC: COSV51821389;