chr19-55401610-G-A

Position:

• chr19-55401610-G-A

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.495C>T​(p.Ala165=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,606,292 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: UBE2S NM_014501.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.77

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=-0.75).
• BP6: Variant 19-55401610-G-A is Benign according to our data. Variant chr19-55401610-G-A is described in ClinVar as [Benign]. Clinvar id is 716611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.77 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (891/152282) while in subpopulation AFR AF= 0.0199 (827/41564). AF 95% confidence interval is 0.0188. There are 10 homozygotes in gnomad4. There are 445 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 891 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2S	NM_014501.3	c.495C>T	p.Ala165=	synonymous_variant	4/4	ENST00000264552.14	NP_055316.2
RPL28	NM_001363697.1	c.325-1333G>A		intron_variant			NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2S	ENST00000264552.14	c.495C>T	p.Ala165=	synonymous_variant	4/4	1	NM_014501.3	ENSP00000264552	P1
UBE2S	ENST00000587845.5	c.582C>T	p.Ala194=	synonymous_variant	5/5	2		ENSP00000467409
RPL28	ENST00000560055.5	c.325-1333G>A		intron_variant		3		ENSP00000452763

Frequencies

GnomAD3 genomes AF: 0.00584 AC: 888 AN: 152164 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00145 AC: 329 AN: 226812 Hom.: 2 AF XY: 0.00116 AC XY: 146 AN XY: 125616

Gnomad AFR exome AF: 0.0199

Gnomad AMR exome AF: 0.00131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000192

Gnomad OTH exome AF: 0.00144

GnomAD4 exome AF: 0.000616 AC: 896 AN: 1454010 Hom.: 10 Cov.: 30 AF XY: 0.000561 AC XY: 406 AN XY: 723128

Gnomad4 AFR exome AF: 0.0195

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.0000194

Gnomad4 NFE exome AF: 0.0000667

Gnomad4 OTH exome AF: 0.00139

GnomAD4 genome AF: 0.00585 AC: 891 AN: 152282 Hom.: 10 Cov.: 32 AF XY: 0.00598 AC XY: 445 AN XY: 74450

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00184 Hom.: 1

Bravo AF: 0.00642

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.82
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs200103438; hg19: chr19-55912978;