rs200312345

Variant summary

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

The NM_005018.3(PDCD1):​c.581G>T​(p.Arg194Leu) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R194Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PDCD1
NM_005018.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0600
Variant links:
Genes affected
PDCD1 (HGNC:8760): (programmed cell death 1) Programmed cell death protein 1 (PDCD1) is an immune-inhibitory receptor expressed in activated T cells; it is involved in the regulation of T-cell functions, including those of effector CD8+ T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into T regulatory cells. PDCD1 is expressed in many types of tumors including melanomas, and has demonstrated to play a role in anti-tumor immunity. Moreover, this protein has been shown to be involved in safeguarding against autoimmunity, however, it can also contribute to the inhibition of effective anti-tumor and anti-microbial immunity. [provided by RefSeq, Aug 2020]

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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=0.19167739).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDCD1NM_005018.3 linkc.581G>T p.Arg194Leu missense_variant Exon 3 of 5 ENST00000334409.10 NP_005009.2 Q15116A0A0M3M0G7
PDCD1XM_006712573.3 linkc.581G>T p.Arg194Leu missense_variant Exon 3 of 4 XP_006712636.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDCD1ENST00000334409.10 linkc.581G>T p.Arg194Leu missense_variant Exon 3 of 5 1 NM_005018.3 ENSP00000335062.5 Q15116
PDCD1ENST00000343705.3 linkc.266-226G>T intron_variant Intron 1 of 2 1 ENSP00000340808.4 H0Y2W6
PDCD1ENST00000418831.1 linkn.*144G>T non_coding_transcript_exon_variant Exon 3 of 5 1 ENSP00000390296.1 E7ER21
PDCD1ENST00000418831.1 linkn.*144G>T 3_prime_UTR_variant Exon 3 of 5 1 ENSP00000390296.1 E7ER21

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000127
AC:
3
AN:
236496
Hom.:
0
AF XY:
0.0000232
AC XY:
3
AN XY:
129264
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000564
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000956
Gnomad OTH exome
AF:
0.000173
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1457410
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
724778
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
7.5
DANN
Benign
0.96
DEOGEN2
Benign
0.37
T
Eigen
Benign
-0.96
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.060
Sift
Uncertain
0.019
D
Sift4G
Benign
0.073
T
Polyphen
0.65
P
Vest4
0.33
MutPred
0.49
Loss of helix (P = 0.0041);
MVP
0.64
MPC
0.43
ClinPred
0.17
T
GERP RS
-4.2
Varity_R
0.066
gMVP
0.51

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.

Other links and lift over

dbSNP: rs200312345; hg19: chr2-242794361; API