Genetic Variant ULBP3:p.Ala84Thr (chr6-150066001-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024518.3(ULBP3):c.250G>A(p.Ala84Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ULBP3
NM_024518.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.664

Variant links:

Genes affected

ULBP3 (HGNC:14895): (UL16 binding protein 3) The protein encoded by this gene is one of several related ligands of the KLRK1/NKG2D receptor, which is found in primary NK cells. Binding of these ligands to the receptor activates several signal transduction pathways, including the JAK2, STAT5, and ERK pathways. The encoded protein is expressed solubly and on the surface of many tumor cells, making it potentially an important target for therapeutics. [provided by RefSeq, Nov 2015]

ULBP3 links:

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ACMG classification

Classification made for transcript

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=0.069282144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULBP3	NM_024518.3 link	c.250G>A	p.Ala84Thr	missense_variant	Exon 2 of 5	ENST00000367339.7	NP_078794.1	Q9BZM4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULBP3	ENST00000367339.7 link	c.250G>A	p.Ala84Thr	missense_variant	Exon 2 of 5	5	NM_024518.3	ENSP00000356308.1		Q9BZM4
ULBP3	ENST00000438272.2 link	c.250G>A	p.Ala84Thr	missense_variant	Exon 2 of 4	1		ENSP00000403562.2		Q9BZM4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251486

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727240

show subpopulations

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.250G>A (p.A84T) alteration is located in exon 2 (coding exon 2) of the ULBP3 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the alanine (A) at amino acid position 84 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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

DANN

Benign

0.68

DEOGEN2

Benign

0.0050

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.45

.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.021

Sift

Benign

0.31

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.17

B;B

Vest4

0.069

MutPred

0.41

Gain of disorder (P = 0.2148);Gain of disorder (P = 0.2148);

MVP

0.26

MPC

0.18

ClinPred

0.073

GERP RS

-3.0

Varity_R

0.050

gMVP

0.066

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over