NM_014501.3:c.504T>G

Variant names:

• chr19-55401601-A-C
• rs111954966
• NM_014501.3:c.504T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014501.3(UBE2S):​c.504T>G​(p.Gly168Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,605,766 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (12 hom., cov: 32)
  • Exomes 𝑓: 0.014 (249 hom.)
• Consequence: UBE2S NM_014501.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.196
• Publications: 1 publications found

Genes affected

UBE2S (HGNC:17895): (ubiquitin conjugating enzyme E2 S) This gene encodes a member of the ubiquitin-conjugating enzyme family. The encoded protein is able to form a thiol ester linkage with ubiquitin in a ubiquitin activating enzyme-dependent manner, a characteristic property of ubiquitin carrier proteins. [provided by RefSeq, Jul 2008]

RPL28 (HGNC:10330): (ribosomal protein L28) 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 L28E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-55401601-A-C is Benign according to our data. Variant chr19-55401601-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 781884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.196 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00935 (1423/152204) while in subpopulation SAS AF = 0.0426 (205/4812). AF 95% confidence interval is 0.0378. There are 12 homozygotes in GnomAd4. There are 732 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1423 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014501.3. 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
	UBE2S	NM_014501.3	MANE Select	c.504T>G	p.Gly168Gly	synonymous	Exon 4 of 4	NP_055316.2	Q16763
	RPL28	NM_001363697.1		c.325-1342A>C		intron	N/A	NP_001350626.1	H0YKD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2S	ENST00000264552.14	TSL:1 MANE Select	c.504T>G	p.Gly168Gly	synonymous	Exon 4 of 4	ENSP00000264552.8	Q16763
	UBE2S	ENST00000917162.1		c.717T>G	p.Gly239Gly	synonymous	Exon 5 of 5	ENSP00000587221.1
	UBE2S	ENST00000587845.5	TSL:2	c.591T>G	p.Gly197Gly	synonymous	Exon 5 of 5	ENSP00000467409.1	K7EPJ1

Frequencies

GnomAD3 genomes AF: 0.00934 AC: 1421 AN: 152090 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.0131 AC: 3022 AN: 229992 AF XY: 0.0149

Gnomad AFR exome AF: 0.00237

Gnomad AMR exome AF: 0.00689

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.0131

Gnomad FIN exome AF: 0.00885

Gnomad NFE exome AF: 0.00973

Gnomad OTH exome AF: 0.00979

GnomAD4 exome AF: 0.0142 AC: 20605 AN: 1453562 Hom.: 249 Cov.: 30 AF XY: 0.0151 AC XY: 10899 AN XY: 722932

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00294 AC: 98 AN: 33328

American (AMR) AF: 0.00702 AC: 309 AN: 43990

Ashkenazi Jewish (ASJ) AF: 0.00189 AC: 49 AN: 25918

East Asian (EAS) AF: 0.0242 AC: 959 AN: 39560

South Asian (SAS) AF: 0.0444 AC: 3814 AN: 85900

European-Finnish (FIN) AF: 0.00898 AC: 464 AN: 51648

Middle Eastern (MID) AF: 0.00363 AC: 16 AN: 4412

European-Non Finnish (NFE) AF: 0.0128 AC: 14160 AN: 1108950

Other (OTH) AF: 0.0123 AC: 736 AN: 59856

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00935 AC: 1423 AN: 152204 Hom.: 12 Cov.: 32 AF XY: 0.00984 AC XY: 732 AN XY: 74414

African (AFR) AF: 0.00320 AC: 133 AN: 41526

American (AMR) AF: 0.00699 AC: 107 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.0161 AC: 83 AN: 5160

South Asian (SAS) AF: 0.0426 AC: 205 AN: 4812

European-Finnish (FIN) AF: 0.00857 AC: 91 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0114 AC: 778 AN: 67996

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00668 Hom.: 3

Bravo AF: 0.00797

ClinVar

ClinVar submissions

Significance: Likely 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	-0.81
CADD	Benign	5.3
DANN	Benign	0.47
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: rs111954966; hg19: chr19-55912969;