13-78616230-A-T

Position:

• chr13-78616230-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024546.4(OBI1):​c.1531T>A​(p.Leu511Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OBI1 NM_024546.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.386

Genes affected

OBI1 (HGNC:20308): (ORC ubiquitin ligase 1) Enables chromatin binding activity and ubiquitin-protein transferase activity. Involved in protein autoubiquitination; protein monoubiquitination; and regulation of DNA replication. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17501509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBI1	NM_024546.4	c.1531T>A	p.Leu511Met	missense_variant	6/6	ENST00000282003.7
OBI1-AS1	NR_047001.1	n.1323A>T		non_coding_transcript_exon_variant	6/6
OBI1	XM_011535225.2	c.1300T>A	p.Leu434Met	missense_variant	5/5
OBI1	XM_024449410.2	c.1300T>A	p.Leu434Met	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBI1	ENST00000282003.7	c.1531T>A	p.Leu511Met	missense_variant	6/6	1	NM_024546.4	P1
OBI1-AS1	ENST00000560584.2	n.1127A>T		non_coding_transcript_exon_variant	4/4	5
OBI1-AS1	ENST00000606429.5	n.1323A>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2023

The c.1531T>A (p.L511M) alteration is located in exon 6 (coding exon 6) of the RNF219 gene. This alteration results from a T to A substitution at nucleotide position 1531, causing the leucine (L) at amino acid position 511 to be replaced by a methionine (M). 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	0.13
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.31
MutPred		0.32		Gain of methylation at K509 (P = 0.0514);
MVP		0.24
MPC		0.26
ClinPred		0.86	D
GERP RS		-1.1
Varity_R		0.32
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-79190365;