19-55404483-A-G

Variant names:

• chr19-55404483-A-G
• rs185239500
• NM_014501.3:c.152-5T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014501.3(UBE2S):​c.152-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UBE2S NM_014501.3 splice_region, intron
• Scores: Splicing: ADA: 0.0003031
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2S	NM_014501.3	c.152-5T>C		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000264552.14	NP_055316.2
UBE2S	XM_011526752.3	c.152-5T>C		splice_region_variant, intron_variant	Intron 2 of 3		XP_011525054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2S	ENST00000264552.14	c.152-5T>C		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_014501.3	ENSP00000264552.8
UBE2S	ENST00000587845.5	c.152-5T>C		splice_region_variant, intron_variant	Intron 2 of 4	2		ENSP00000467409.1
UBE2S	ENST00000589978.1	c.152-82T>C		intron_variant	Intron 2 of 3	5		ENSP00000466388.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.1
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.098
SpliceAI score (max)		0.050		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: rs185239500; hg19: chr19-55915851;