9-33922599-T-C

Variant names:

• chr9-33922599-T-C
• rs556932450
• NM_001370062.2:c.3265A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370062.2(UBAP2):​c.3265A>G​(p.Ser1089Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1089C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: UBAP2 NM_001370062.2 missense, splice_region
• Scores: Splicing: ADA: 0.0003850
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 1 publications found

Genes affected

UBAP2 (HGNC:14185): (ubiquitin associated protein 2) The protein encoded by this gene contains a UBA (ubiquitin associated) domain, which is characteristic of proteins that function in the ubiquitination pathway. This gene may show increased expression in the adrenal gland and lymphatic tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041880816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370062.2. 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
	UBAP2	NM_001370062.2	MANE Select	c.3265A>G	p.Ser1089Gly	missense splice_region	Exon 29 of 29	NP_001356991.2	Q5T6F2-1
	UBAP2	NM_001370059.2		c.3265A>G	p.Ser1089Gly	missense splice_region	Exon 29 of 29	NP_001356988.2	Q5T6F2-1
	UBAP2	NM_018449.4		c.3265A>G	p.Ser1089Gly	missense splice_region	Exon 29 of 29	NP_060919.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP2	ENST00000379238.7	TSL:5 MANE Select	c.3265A>G	p.Ser1089Gly	missense splice_region	Exon 29 of 29	ENSP00000368540.2	Q5T6F2-1
	UBAP2	ENST00000379235.5	TSL:1	n.1933A>G		splice_region non_coding_transcript_exon	Exon 10 of 10
	UBAP2	ENST00000862381.1		c.3388A>G	p.Ser1130Gly	missense splice_region	Exon 30 of 30	ENSP00000532440.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74300

African (AFR) AF: 0.0000483 AC: 2 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

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

Alfa AF: 0.0000278 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.055	N
PhyloP100		1.9
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.12
Sift	Benign	0.47	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.032
MVP		0.043
MPC		0.061
ClinPred		0.29	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.21
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.060		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: rs556932450; hg19: chr9-33922597;