19-55406848-G-C

Variant names:

• chr19-55406848-G-C
• rs1251231304
• NM_014501.3:c.118C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014501.3(UBE2S):​c.118C>G​(p.Leu40Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBE2S NM_014501.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19237554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2S	NM_014501.3	c.118C>G	p.Leu40Val	missense_variant	Exon 2 of 4	ENST00000264552.14	NP_055316.2
UBE2S	XM_011526752.3	c.118C>G	p.Leu40Val	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.118C>G	p.Leu40Val	missense_variant	Exon 2 of 4	1	NM_014501.3	ENSP00000264552.8
UBE2S	ENST00000587845.5	c.118C>G	p.Leu40Val	missense_variant	Exon 2 of 5	2		ENSP00000467409.1
UBE2S	ENST00000589978.1	c.118C>G	p.Leu40Val	missense_variant	Exon 2 of 4	5		ENSP00000466388.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461404 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726994

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118C>G (p.L40V) alteration is located in exon 2 (coding exon 2) of the UBE2S gene. This alteration results from a C to G substitution at nucleotide position 118, causing the leucine (L) at amino acid position 40 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.062	T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.50	N;.;.
REVEL	Benign	0.071
Sift	Benign	0.65	T;.;.
Sift4G	Benign	0.47	T;.;T
Polyphen		0.0	B;.;.
Vest4		0.30
MutPred		0.57		Gain of disorder (P = 0.2515);Gain of disorder (P = 0.2515);Gain of disorder (P = 0.2515);
MVP		0.52
MPC		1.1
ClinPred		0.70	D
GERP RS		3.7
Varity_R		0.18
gMVP		0.89

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: rs1251231304; hg19: chr19-55918216;