NM_014501.3:c.116A>G

Variant names:

• chr19-55406850-T-C
• rs770350118
• NM_014501.3:c.116A>G

Variant summary

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

The NM_014501.3(UBE2S):​c.116A>G​(p.Asp39Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UBE2S NM_014501.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.05

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, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2S	NM_014501.3	c.116A>G	p.Asp39Gly	missense_variant	Exon 2 of 4	ENST00000264552.14	NP_055316.2
UBE2S	XM_011526752.3	c.116A>G	p.Asp39Gly	missense_variant	Exon 2 of 4		XP_011525054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2S	ENST00000264552.14	c.116A>G	p.Asp39Gly	missense_variant	Exon 2 of 4	1	NM_014501.3	ENSP00000264552.8
UBE2S	ENST00000587845.5	c.116A>G	p.Asp39Gly	missense_variant	Exon 2 of 5	2		ENSP00000467409.1
UBE2S	ENST00000589978.1	c.116A>G	p.Asp39Gly	missense_variant	Exon 2 of 4	5		ENSP00000466388.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

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	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.7	H;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.3	D;.;.
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0050	D;.;.
Sift4G	Uncertain	0.011	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.93
MutPred		0.59		Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);
MVP		0.89
MPC		2.6
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.90
gMVP		0.94

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: rs770350118; hg19: chr19-55918218;