rs139865016

Variant names:

• chr6-150064701-A-G
• rs139865016
• NM_024518.3:c.641T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-150064701-A-G
• chr6-150064701-A-C

Variant summary

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

The NM_024518.3(ULBP3):​c.641T>C​(p.Met214Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,614,034 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00060 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (1 hom.)
• Consequence: ULBP3 NM_024518.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.66
• Publications: 4 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=0.004831016).

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.641T>C	p.Met214Thr	missense	Exon 4 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.641T>C	p.Met214Thr	missense	Exon 4 of 5	ENSP00000356308.1	Q9BZM4
	ULBP3	ENST00000438272.2	TSL:1	c.641T>C	p.Met214Thr	missense	Exon 4 of 4	ENSP00000403562.2	Q9BZM4
	ULBP3	ENST00000925509.1		c.494T>C	p.Met165Thr	missense	Exon 4 of 5	ENSP00000595568.1

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 251320 AF XY: 0.000125

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000711 AC: 104 AN: 1461748 Hom.: 1 Cov.: 33 AF XY: 0.0000743 AC XY: 54 AN XY: 727166

African (AFR) AF: 0.00248 AC: 83 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111908

Other (OTH) AF: 0.000149 AC: 9 AN: 60392

GnomAD4 genome AF: 0.000598 AC: 91 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74472

African (AFR) AF: 0.00204 AC: 85 AN: 41568

American (AMR) AF: 0.000262 AC: 4 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000507 Hom.: 0

Bravo AF: 0.000627

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000206 AC: 25

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

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	0.069
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.011
DANN	Benign	0.14
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.081	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.92	T
PhyloP100		-1.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	0.66	T
Polyphen		0.0020	B
Vest4		0.041
MVP		0.067
MPC		0.17
ClinPred		0.0049	T
GERP RS		-5.7
Varity_R		0.019
gMVP		0.11
Mutation Taster		=100/0	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: rs139865016; hg19: chr6-150385837;