15-74452328-C-G

Variant names:

• chr15-74452328-C-G
• rs1000045651
• NM_032907.5:c.355G>C

Variant summary

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

The NM_032907.5(UBL7):​c.355G>C​(p.Ala119Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A119T) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UBL7 NM_032907.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02
• Publications: 0 publications found

Genes affected

UBL7 (HGNC:28221): (ubiquitin like 7) Predicted to enable polyubiquitin modification-dependent protein binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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_032907.5. 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
	UBL7	NM_032907.5	MANE Select	c.355G>C	p.Ala119Pro	missense	Exon 4 of 11	NP_116296.1	Q96S82
	UBL7	NM_001286741.2		c.475G>C	p.Ala159Pro	missense	Exon 4 of 11	NP_001273670.1
	UBL7	NM_001286742.2		c.475G>C	p.Ala159Pro	missense	Exon 5 of 12	NP_001273671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL7	ENST00000395081.7	TSL:1 MANE Select	c.355G>C	p.Ala119Pro	missense	Exon 4 of 11	ENSP00000378518.2	Q96S82
	UBL7	ENST00000564488.5	TSL:1	c.355G>C	p.Ala119Pro	missense	Exon 5 of 12	ENSP00000454828.1	Q96S82
	UBL7	ENST00000565335.5	TSL:1	c.355G>C	p.Ala119Pro	missense	Exon 5 of 12	ENSP00000457708.1	Q96S82

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.79
MutPred		0.48		Gain of disorder (P = 0.0416)
MVP		0.72
MPC		1.0
ClinPred		0.93	D
GERP RS		4.5
PromoterAI		0.0024	Neutral
Varity_R		0.76
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1000045651; hg19: chr15-74744669;