chr15-74456627-C-T

Variant names:

• chr15-74456627-C-T
• rs1284099268
• NM_032907.5:c.229G>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.229G>A​(p.Asp77Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. D77H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UBL7 NM_032907.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• 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=0.39683414).

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.229G>A	p.Asp77Asn	missense	Exon 3 of 11	NP_116296.1	Q96S82
	UBL7	NM_001286741.2		c.349G>A	p.Asp117Asn	missense	Exon 3 of 11	NP_001273670.1
	UBL7	NM_001286742.2		c.349G>A	p.Asp117Asn	missense	Exon 4 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.229G>A	p.Asp77Asn	missense	Exon 3 of 11	ENSP00000378518.2	Q96S82
	UBL7	ENST00000564488.5	TSL:1	c.229G>A	p.Asp77Asn	missense	Exon 4 of 12	ENSP00000454828.1	Q96S82
	UBL7	ENST00000565335.5	TSL:1	c.229G>A	p.Asp77Asn	missense	Exon 4 of 12	ENSP00000457708.1	Q96S82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Benign	0.20	T
Sift4G	Uncertain	0.028	D
Polyphen		0.80	P
Vest4		0.62
MutPred		0.30		Gain of catalytic residue at D77 (P = 0.0444)
MVP		0.81
MPC		0.33
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.25
gMVP		0.47
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1284099268; hg19: chr15-74748968; COSMIC: COSV108213044; COSMIC: COSV108213044;