chr15-74452328-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBL7	NM_032907.5	c.355G>A	p.Ala119Thr	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.355G>A	p.Ala119Thr	missense_variant	Exon 4 of 11	1	NM_032907.5	ENSP00000378518.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000250

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

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.355G>A (p.A119T) alteration is located in exon 4 (coding exon 3) of the UBL7 gene. This alteration results from a G to A substitution at nucleotide position 355, causing the alanine (A) at amino acid position 119 to be replaced by a threonine (T). 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	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;T;T;T;T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;.;.;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.080	T;T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T;.
Polyphen		0.21	B;B;B;B;B;.
Vest4		0.60
MutPred		0.48		Gain of catalytic residue at A119 (P = 0.0135);Gain of catalytic residue at A119 (P = 0.0135);Gain of catalytic residue at A119 (P = 0.0135);Gain of catalytic residue at A119 (P = 0.0135);Gain of catalytic residue at A119 (P = 0.0135);Gain of catalytic residue at A119 (P = 0.0135);
MVP		0.57
MPC		0.89
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs1000045651; hg19: chr15-74744669;