NM_025239.4:c.164T>A

Variant names:

• chr9-5534853-T-A
• NM_025239.4:c.164T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025239.4(PDCD1LG2):​c.164T>A​(p.Ile55Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD1LG2 NM_025239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

Genes affected

PDCD1LG2 (HGNC:18731): (programmed cell death 1 ligand 2) Involved in negative regulation of activated T cell proliferation; negative regulation of interferon-gamma production; and negative regulation of interleukin-10 production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. Biomarker of pulmonary tuberculosis. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286162 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD1LG2	NM_025239.4	c.164T>A	p.Ile55Lys	missense_variant	Exon 3 of 7	ENST00000397747.5	NP_079515.2
PDCD1LG2	XM_005251600.4	c.164T>A	p.Ile55Lys	missense_variant	Exon 3 of 7		XP_005251657.1
LOC124902114	XR_007061406.1	n.162-10224A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD1LG2	ENST00000397747.5	c.164T>A	p.Ile55Lys	missense_variant	Exon 3 of 7	1	NM_025239.4	ENSP00000380855.3
ENSG00000286162	ENST00000661858.1	n.183-10224A>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.70	P
Vest4		0.48
MutPred		0.77		Gain of disorder (P = 0.0037);
MVP		0.42
MPC		0.22
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.76
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-5534853;