15-74452342-C-G

Variant names:

• chr15-74452342-C-G
• rs749570682
• NM_032907.5:c.341G>C

Variant summary

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

The NM_032907.5(UBL7):​c.341G>C​(p.Arg114Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,409,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: UBL7 NM_032907.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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

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
UBL7	NM_032907.5	c.341G>C	p.Arg114Pro	missense_variant	Exon 4 of 11	ENST00000395081.7	NP_116296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBL7	ENST00000395081.7	c.341G>C	p.Arg114Pro	missense_variant	Exon 4 of 11	1	NM_032907.5	ENSP00000378518.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000581 AC: 1 AN: 171976 Hom.: 0 AF XY: 0.0000110 AC XY: 1 AN XY: 91008

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1409424 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 696036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000270

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341G>C (p.R114P) alteration is located in exon 4 (coding exon 3) of the UBL7 gene. This alteration results from a G to C substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T;T;T;T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;.;.;.;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M;M;M;M;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.14	T;T;T;T;T;D
Sift4G	Benign	0.11	T;T;T;T;T;.
Polyphen		1.0	D;D;D;D;D;.
Vest4		0.76
MutPred		0.58		Loss of MoRF binding (P = 0.0129);Loss of MoRF binding (P = 0.0129);Loss of MoRF binding (P = 0.0129);Loss of MoRF binding (P = 0.0129);Loss of MoRF binding (P = 0.0129);Loss of MoRF binding (P = 0.0129);
MVP		0.66
MPC		1.1
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.61
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749570682; hg19: chr15-74744683;