19-55404476-C-T

Variant names:

• chr19-55404476-C-T
• NM_014501.3:c.154G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014501.3(UBE2S):​c.154G>A​(p.Gly52Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000688 in 1,452,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UBE2S NM_014501.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2S	NM_014501.3	c.154G>A	p.Gly52Arg	missense_variant, splice_region_variant	Exon 3 of 4	ENST00000264552.14	NP_055316.2
UBE2S	XM_011526752.3	c.154G>A	p.Gly52Arg	missense_variant, splice_region_variant	Exon 3 of 4		XP_011525054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2S	ENST00000264552.14	c.154G>A	p.Gly52Arg	missense_variant, splice_region_variant	Exon 3 of 4	1	NM_014501.3	ENSP00000264552.8
UBE2S	ENST00000587845.5	c.154G>A	p.Gly52Arg	missense_variant, splice_region_variant	Exon 3 of 5	2		ENSP00000467409.1
UBE2S	ENST00000589978.1	c.152-75G>A		intron_variant	Intron 2 of 3	5		ENSP00000466388.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	3.9	H;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.5	D;.
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0030	D;.
Polyphen		1.0	D;.
Vest4		0.85
MutPred		0.68		Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP		0.84
MPC		2.5
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-55915844;