15-65102153-T-C

Variant names:

• chr15-65102153-T-C
• rs923123336
• NM_001163692.2:c.652A>G

Variant summary

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

The NM_001163692.2(UBAP1L):​c.652A>G​(p.Thr218Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,202,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. T218M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.420
• 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=0.07405171).

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.652A>G	p.Thr218Ala	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.652A>G	p.Thr218Ala	missense	Exon 3 of 6	ENSP00000454012.1	F5GYI3
	UBAP1L	ENST00000907325.1		c.652A>G	p.Thr218Ala	missense	Exon 2 of 5	ENSP00000577384.1
	UBAP1L	ENST00000558802.1	TSL:5	n.240+412A>G		intron	N/A	ENSP00000452794.1	H0YKG2

Frequencies

GnomAD3 genomes AF: 0.000595 AC: 89 AN: 149568 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.000974

GnomAD4 exome AF: 0.000436 AC: 459 AN: 1053044 Hom.: 0 Cov.: 29 AF XY: 0.000440 AC XY: 219 AN XY: 497442

African (AFR) AF: 0.00 AC: 0 AN: 21634

American (AMR) AF: 0.00 AC: 0 AN: 7520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12994

East Asian (EAS) AF: 0.00 AC: 0 AN: 24212

South Asian (SAS) AF: 0.00 AC: 0 AN: 19452

European-Finnish (FIN) AF: 0.00198 AC: 41 AN: 20696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2738

European-Non Finnish (NFE) AF: 0.000451 AC: 407 AN: 902230

Other (OTH) AF: 0.000265 AC: 11 AN: 41568

GnomAD4 genome AF: 0.000595 AC: 89 AN: 149666 Hom.: 0 Cov.: 32 AF XY: 0.000739 AC XY: 54 AN XY: 73032

African (AFR) AF: 0.00 AC: 0 AN: 40880

American (AMR) AF: 0.00 AC: 0 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.00 AC: 0 AN: 4734

European-Finnish (FIN) AF: 0.00131 AC: 13 AN: 9944

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

European-Non Finnish (NFE) AF: 0.00110 AC: 74 AN: 67180

Other (OTH) AF: 0.000963 AC: 2 AN: 2076

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.000393

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	0.22
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.42
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.010
Sift	Benign	0.14	T
Sift4G	Benign	0.099	T
Polyphen		0.30	B
Vest4		0.074
MVP		0.014
ClinPred		0.37	T
GERP RS		1.8
Varity_R		0.094
gMVP		0.47
Mutation Taster		=90/10	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: rs923123336; hg19: chr15-65394491; COSMIC: COSV101544066; COSMIC: COSV101544066;