rs765784409

Variant names:

• chr12-108623772-G-A
• rs765784409
• NM_003006.4:c.536C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-108623772-G-A
• chr12-108623772-G-C

Variant summary

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

The NM_003006.4(SELPLG):​c.536C>T​(p.Thr179Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: SELPLG NM_003006.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• Publications: 1 publications found

Genes affected

SELPLG (HGNC:10722): (selectin P ligand) This gene encodes a glycoprotein that functions as a high affinity counter-receptor for the cell adhesion molecules P-, E- and L- selectin expressed on myeloid cells and stimulated T lymphocytes. As such, this protein plays a critical role in leukocyte trafficking during inflammation by tethering of leukocytes to activated platelets or endothelia expressing selectins. This protein requires two post-translational modifications, tyrosine sulfation and the addition of the sialyl Lewis x tetrasaccharide (sLex) to its O-linked glycans, for its high-affinity binding activity. Aberrant expression of this gene and polymorphisms in this gene are associated with defects in the innate and adaptive immune response. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.10102433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003006.4. 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
	SELPLG	NM_003006.4	MANE Select	c.536C>T	p.Thr179Met	missense	Exon 2 of 2	NP_002997.2	Q14242-1
	SELPLG	NM_001206609.2		c.584C>T	p.Thr195Met	missense	Exon 2 of 2	NP_001193538.1	Q14242-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELPLG	ENST00000550948.2	TSL:1 MANE Select	c.536C>T	p.Thr179Met	missense	Exon 2 of 2	ENSP00000447752.1	Q14242-1
	SELPLG	ENST00000228463.7	TSL:2	c.584C>T	p.Thr195Met	missense	Exon 2 of 2	ENSP00000228463.6	Q14242-2
	SELPLG	ENST00000884614.1		c.536C>T	p.Thr179Met	missense	Exon 2 of 2	ENSP00000554673.1

Frequencies

GnomAD3 genomes AF: 0.0000595 AC: 9 AN: 151322 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000219

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251278 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461014 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20 AN XY: 726778

African (AFR) AF: 0.0000300 AC: 1 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 44672

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111634

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome AF: 0.0000595 AC: 9 AN: 151322 Hom.: 0 Cov.: 32 AF XY: 0.0000406 AC XY: 3 AN XY: 73872

African (AFR) AF: 0.000219 AC: 9 AN: 41136

American (AMR) AF: 0.00 AC: 0 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67816

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000242 Hom.: 0

ExAC AF: 0.0000330 AC: 4

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	0.090
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Benign	0.77
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PhyloP100		-1.3
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.051
Sift	Benign	0.26	T
Sift4G	Benign	0.12	T
Polyphen		0.94	P
Vest4		0.10
MutPred		0.34		Gain of catalytic residue at P175 (P = 0.0011)
MVP		0.51
MPC		0.11
ClinPred		0.062	T
GERP RS		1.6
Varity_R		0.017
gMVP		0.20
Mutation Taster		=92/8	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: rs765784409; hg19: chr12-109017548;