19-55401601-A-C

Position:

• chr19-55401601-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_014501.3(UBE2S):​c.504T>G​(p.Gly168=) 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, single submitter B:1
• Conservation: PhyloP100: 0.196

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 -15 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 id is 781884.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1423 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2S	NM_014501.3	c.504T>G	p.Gly168=	synonymous_variant	4/4	ENST00000264552.14
RPL28	NM_001363697.1	c.325-1342A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2S	ENST00000264552.14	c.504T>G	p.Gly168=	synonymous_variant	4/4	1	NM_014501.3	P1
UBE2S	ENST00000587845.5	c.591T>G	p.Gly197=	synonymous_variant	5/5	2
RPL28	ENST00000560055.5	c.325-1342A>C		intron_variant		3

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

GnomAD3 exomes AF: 0.0131 AC: 3022 AN: 229992 Hom.: 50 AF XY: 0.0149 AC XY: 1900 AN XY: 127252

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 SAS exome AF: 0.0434

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

Gnomad4 AFR exome AF: 0.00294

Gnomad4 AMR exome AF: 0.00702

Gnomad4 ASJ exome AF: 0.00189

Gnomad4 EAS exome AF: 0.0242

Gnomad4 SAS exome AF: 0.0444

Gnomad4 FIN exome AF: 0.00898

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0123

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

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.00699

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0161

Gnomad4 SAS AF: 0.0426

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00668 Hom.: 3

Bravo AF: 0.00797

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 02, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.47

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: rs111954966; hg19: chr19-55912969;