chr19-55401541-C-T

Position:

• chr19-55401541-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014501.3(UBE2S):​c.564G>A​(p.Pro188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,610,658 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (18 hom.)
• Consequence: UBE2S NM_014501.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.60

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-55401541-C-T is Benign according to our data. Variant chr19-55401541-C-T is described in ClinVar as [Benign]. Clinvar id is 783852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.6 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1696/152240) while in subpopulation AFR AF= 0.0378 (1570/41546). AF 95% confidence interval is 0.0362. There are 22 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1696 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2S	NM_014501.3	c.564G>A	p.Pro188=	synonymous_variant	4/4	ENST00000264552.14	NP_055316.2
RPL28	NM_001363697.1	c.325-1402C>T		intron_variant			NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2S	ENST00000264552.14	c.564G>A	p.Pro188=	synonymous_variant	4/4	1	NM_014501.3	ENSP00000264552	P1
RPL28	ENST00000560055.5	c.325-1402C>T		intron_variant		3		ENSP00000452763
UBE2S	ENST00000587845.5			downstream_gene_variant		2		ENSP00000467409

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1687 AN: 152122 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00282 AC: 684 AN: 242880 Hom.: 10 AF XY: 0.00224 AC XY: 298 AN XY: 133106

Gnomad AFR exome AF: 0.0413

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000156

Gnomad OTH exome AF: 0.00302

GnomAD4 exome AF: 0.00119 AC: 1741 AN: 1458418 Hom.: 18 Cov.: 29 AF XY: 0.000998 AC XY: 724 AN XY: 725554

Gnomad4 AFR exome AF: 0.0397

Gnomad4 AMR exome AF: 0.00242

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.00294

GnomAD4 genome AF: 0.0111 AC: 1696 AN: 152240 Hom.: 22 Cov.: 32 AF XY: 0.0108 AC XY: 802 AN XY: 74428

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00360 Hom.: 2

Bravo AF: 0.0132

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs114808768; hg19: chr19-55912909;