chr6-150065629-C-T

Variant names:

• chr6-150065629-C-T
• rs762480458
• NM_024518.3:c.397G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024518.3(ULBP3):​c.397G>A​(p.Asp133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: ULBP3 NM_024518.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032615066).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024518.3. 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
	ULBP3	NM_024518.3	MANE Select	c.397G>A	p.Asp133Asn	missense	Exon 3 of 5	NP_078794.1	Q9BZM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULBP3	ENST00000367339.7	TSL:5 MANE Select	c.397G>A	p.Asp133Asn	missense	Exon 3 of 5	ENSP00000356308.1	Q9BZM4
	ULBP3	ENST00000438272.2	TSL:1	c.397G>A	p.Asp133Asn	missense	Exon 3 of 4	ENSP00000403562.2	Q9BZM4
	ULBP3	ENST00000925509.1		c.250G>A	p.Asp84Asn	missense	Exon 3 of 5	ENSP00000595568.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251482 AF XY: 0.000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000272

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000869 AC: 127 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.0000880 AC XY: 64 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000935 AC: 104 AN: 1112008

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

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

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.000173 AC: 21

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	0.091
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.060
DANN	Benign	0.64
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.94	T
PhyloP100		-1.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.026
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Polyphen		0.047	B
Vest4		0.18
MVP		0.20
MPC		0.13
ClinPred		0.0080	T
GERP RS		-4.3
Varity_R		0.057
gMVP		0.068
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs762480458; hg19: chr6-150386765; COSMIC: COSV108220600;