rs758247000

Variant names:

• chr11-118371586-A-C
• NM_001204077.2:c.481A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-118371586-A-C
• chr11-118371586-A-G

Variant summary

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

The NM_001204077.2(UBE4A):​c.481A>C​(p.Asn161His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UBE4A NM_001204077.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95

Genes affected

UBE4A (HGNC:12499): (ubiquitination factor E4A) This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.481A>C	p.Asn161His	missense_variant	Exon 5 of 20	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4	c.481A>C	p.Asn161His	missense_variant	Exon 5 of 20		NP_004779.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8	c.481A>C	p.Asn161His	missense_variant	Exon 5 of 20	1	NM_001204077.2	ENSP00000252108.4
UBE4A	ENST00000431736.6	c.481A>C	p.Asn161His	missense_variant	Exon 5 of 20	1		ENSP00000387362.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461726 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727160

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		1.0	D;D
Vest4		0.84
MutPred		0.27		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.27
MPC		1.0
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.47

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: chr11-118242301;