rs1167059127

Variant names:

• chr15-65102152-G-A
• rs1167059127
• NM_001163692.2:c.653C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-65102152-G-A
• chr15-65102152-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001163692.2(UBAP1L):​c.653C>T​(p.Thr218Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,209,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T218A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04
• Publications: 0 publications found

Genes affected

UBAP1L (HGNC:40028): (ubiquitin associated protein 1 like) Predicted to enable ubiquitin binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP1L Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• retinal degeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.113060385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163692.2. 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
	UBAP1L	NM_001163692.2	MANE Select	c.653C>T	p.Thr218Met	missense	Exon 3 of 6	NP_001157164.1	F5GYI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1L	ENST00000559089.6	TSL:1 MANE Select	c.653C>T	p.Thr218Met	missense	Exon 3 of 6	ENSP00000454012.1	F5GYI3
	UBAP1L	ENST00000907325.1		c.653C>T	p.Thr218Met	missense	Exon 2 of 5	ENSP00000577384.1
	UBAP1L	ENST00000558802.1	TSL:5	n.240+413C>T		intron	N/A	ENSP00000452794.1	H0YKG2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151808 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000359 AC: 38 AN: 1057176 Hom.: 0 Cov.: 29 AF XY: 0.0000280 AC XY: 14 AN XY: 499460

African (AFR) AF: 0.00 AC: 0 AN: 21840

American (AMR) AF: 0.00 AC: 0 AN: 7674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13188

East Asian (EAS) AF: 0.00126 AC: 31 AN: 24600

South Asian (SAS) AF: 0.0000513 AC: 1 AN: 19492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2772

European-Non Finnish (NFE) AF: 0.00000332 AC: 3 AN: 904856

Other (OTH) AF: 0.0000716 AC: 3 AN: 41904

GnomAD4 genome AF: 0.000105 AC: 16 AN: 151918 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74264

African (AFR) AF: 0.0000241 AC: 1 AN: 41520

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000155

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.086
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.16
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.14		Loss of phosphorylation at T218 (P = 0.0044)
MVP		0.040
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.054
gMVP		0.50
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1167059127; hg19: chr15-65394490; COSMIC: COSV108967104; COSMIC: COSV108967104;