NM_014501.3:c.188A>C

Variant names:

• chr19-55404442-T-G
• rs1415474642
• NM_014501.3:c.188A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014501.3(UBE2S):​c.188A>C​(p.Lys63Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,611,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UBE2S NM_014501.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014501.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2S	NM_014501.3	MANE Select	c.188A>C	p.Lys63Thr	missense	Exon 3 of 4	NP_055316.2	Q16763

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2S	ENST00000264552.14	TSL:1 MANE Select	c.188A>C	p.Lys63Thr	missense	Exon 3 of 4	ENSP00000264552.8	Q16763
	UBE2S	ENST00000917162.1		c.401A>C	p.Lys134Thr	missense	Exon 4 of 5	ENSP00000587221.1
	UBE2S	ENST00000587845.5	TSL:2	c.188A>C	p.Lys63Thr	missense	Exon 3 of 5	ENSP00000467409.1	K7EPJ1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151968 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459794 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726050

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 85980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110814

Other (OTH) AF: 0.00 AC: 0 AN: 60298

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151968 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74218

African (AFR) AF: 0.00 AC: 0 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.42		Loss of ubiquitination at K63 (P = 0.0496)
MVP		0.68
MPC		2.5
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.93
gMVP		0.88
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1415474642; hg19: chr19-55915810;