15-74452342-C-T

Variant names:

• chr15-74452342-C-T
• rs749570682
• NM_032907.5:c.341G>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.341G>A​(p.Arg114Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,409,424 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. R114P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UBL7 NM_032907.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• 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=0.30503702).

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.341G>A	p.Arg114Gln	missense	Exon 4 of 11	NP_116296.1	Q96S82
	UBL7	NM_001286741.2		c.461G>A	p.Arg154Gln	missense	Exon 4 of 11	NP_001273670.1
	UBL7	NM_001286742.2		c.461G>A	p.Arg154Gln	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.341G>A	p.Arg114Gln	missense	Exon 4 of 11	ENSP00000378518.2	Q96S82
	UBL7	ENST00000564488.5	TSL:1	c.341G>A	p.Arg114Gln	missense	Exon 5 of 12	ENSP00000454828.1	Q96S82
	UBL7	ENST00000565335.5	TSL:1	c.341G>A	p.Arg114Gln	missense	Exon 5 of 12	ENSP00000457708.1	Q96S82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000581 AC: 1 AN: 171976 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000144

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1409424 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 696036

African (AFR) AF: 0.00 AC: 0 AN: 32430

American (AMR) AF: 0.00 AC: 0 AN: 37090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25258

East Asian (EAS) AF: 0.00 AC: 0 AN: 37124

South Asian (SAS) AF: 0.00 AC: 0 AN: 80098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1083754

Other (OTH) AF: 0.00 AC: 0 AN: 58344

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000866 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.12
Sift	Benign	0.30	T
Sift4G	Benign	0.33	T
Polyphen		0.83	P
Vest4		0.36
MutPred		0.49		Loss of MoRF binding (P = 0.0396)
MVP		0.44
MPC		0.76
ClinPred		0.76	D
GERP RS		5.5
PromoterAI		-0.15	Neutral
Varity_R		0.16
gMVP		0.61
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs749570682; hg19: chr15-74744683;