9-33922874-A-G

Variant names:

• chr9-33922874-A-G
• rs776429442
• NM_001370062.2:c.3077T>C

Variant summary

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

The NM_001370062.2(UBAP2):​c.3077T>C​(p.Phe1026Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,445,344 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: 0.0000021 (0 hom.)
• Consequence: UBAP2 NM_001370062.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95

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

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
UBAP2	NM_001370062.2	c.3077T>C	p.Phe1026Ser	missense_variant	Exon 28 of 29	ENST00000379238.7	NP_001356991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP2	ENST00000379238.7	c.3077T>C	p.Phe1026Ser	missense_variant	Exon 28 of 29	5	NM_001370062.2	ENSP00000368540.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000124 AC: 3 AN: 242786 Hom.: 0 AF XY: 0.0000153 AC XY: 2 AN XY: 131100

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000344

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1445344 Hom.: 0 Cov.: 33 AF XY: 0.00000279 AC XY: 2 AN XY: 716696

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.80	T;.;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.8	.;D;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.57	T;T;T
Polyphen		0.99	.;D;D
Vest4		0.98
MutPred		0.44		.;Loss of catalytic residue at F1026 (P = 0.0058);Loss of catalytic residue at F1026 (P = 0.0058);
MVP		0.44
MPC		0.11
ClinPred		0.95	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs776429442; hg19: chr9-33922872;