chr1-159829881-C-A

Variant summary

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

The NM_020125.3(SLAMF8):​c.56C>A​(p.Thr19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,484 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. 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. T19I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLAMF8
NM_020125.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.205
Variant links:
Genes affected
SLAMF8 (HGNC:21391): (SLAM family member 8) This gene encodes a member of the CD2 family of cell surface proteins involved in lymphocyte activation. These proteins are characterized by Ig domains. This protein is expressed in lymphoid tissues, and studies of a similar protein in mouse suggest that it may function during B cell lineage commitment. The gene is found in a region of chromosome 1 containing many CD2 genes. [provided by RefSeq, Jul 2008]

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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=0.07666713).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLAMF8NM_020125.3 linkc.56C>A p.Thr19Lys missense_variant Exon 2 of 5 ENST00000289707.10 NP_064510.1 Q9P0V8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLAMF8ENST00000289707.10 linkc.56C>A p.Thr19Lys missense_variant Exon 2 of 5 1 NM_020125.3 ENSP00000289707.5 Q9P0V8-1
SLAMF8ENST00000368104.4 linkc.40+2943C>A intron_variant Intron 1 of 3 2 ENSP00000357084.4 Q9P0V8-2
SLAMF8ENST00000471286.5 linkn.-127C>A upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458484
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
725348
show subpopulations
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
8.1
DANN
Benign
0.89
DEOGEN2
Benign
0.019
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.077
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.037
Sift
Benign
0.067
T
Sift4G
Benign
0.069
T
Polyphen
0.040
B
Vest4
0.22
MutPred
0.49
Gain of ubiquitination at T19 (P = 0.0219);
MVP
0.085
MPC
0.068
ClinPred
0.11
T
GERP RS
-0.42
Varity_R
0.050
gMVP
0.40

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: chr1-159799671; API