chr15-74452328-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032907.5(UBL7):​c.355G>A​(p.Ala119Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,408,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UBL7 NM_032907.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38910443).

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>A	p.Ala119Thr	missense	Exon 4 of 11	NP_116296.1	Q96S82
	UBL7	NM_001286741.2		c.475G>A	p.Ala159Thr	missense	Exon 4 of 11	NP_001273670.1
	UBL7	NM_001286742.2		c.475G>A	p.Ala159Thr	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>A	p.Ala119Thr	missense	Exon 4 of 11	ENSP00000378518.2	Q96S82
	UBL7	ENST00000564488.5	TSL:1	c.355G>A	p.Ala119Thr	missense	Exon 5 of 12	ENSP00000454828.1	Q96S82
	UBL7	ENST00000565335.5	TSL:1	c.355G>A	p.Ala119Thr	missense	Exon 5 of 12	ENSP00000457708.1	Q96S82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1408310 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 695356

African (AFR) AF: 0.00 AC: 0 AN: 32354

American (AMR) AF: 0.00 AC: 0 AN: 36934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25248

East Asian (EAS) AF: 0.00 AC: 0 AN: 37028

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 79982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083168

Other (OTH) AF: 0.00 AC: 0 AN: 58302

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.080	T
Sift4G	Benign	0.13	T
Polyphen		0.21	B
Vest4		0.60
MutPred		0.48		Gain of catalytic residue at A119 (P = 0.0135)
MVP		0.57
MPC		0.89
ClinPred		0.91	D
GERP RS		4.5
PromoterAI		-0.018	Neutral
Varity_R		0.16
gMVP		0.55
Mutation Taster		=39/61	disease causing

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

Other links and lift over

dbSNP: rs1000045651; hg19: chr15-74744669;