chr1-159833037-C-T

Variant summary

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

The NM_020125.3(SLAMF8):​c.529C>T​(p.His177Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLAMF8
NM_020125.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.108
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]

Genome browser will be placed here

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=0.083116055).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLAMF8NM_020125.3 linkc.529C>T p.His177Tyr missense_variant Exon 3 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.529C>T p.His177Tyr missense_variant Exon 3 of 5 1 NM_020125.3 ENSP00000289707.5 Q9P0V8-1
SLAMF8ENST00000368104.4 linkc.202C>T p.His68Tyr missense_variant Exon 2 of 4 2 ENSP00000357084.4 Q9P0V8-2
SLAMF8ENST00000471286.5 linkn.347C>T non_coding_transcript_exon_variant Exon 2 of 4 3
SLAMF8ENST00000497141.1 linkn.33C>T non_coding_transcript_exon_variant Exon 1 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251488
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.529C>T (p.H177Y) alteration is located in exon 3 (coding exon 3) of the SLAMF8 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the histidine (H) at amino acid position 177 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
6.8
DANN
Benign
0.96
DEOGEN2
Benign
0.0056
T;.
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.083
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
M;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.47
N;N
REVEL
Benign
0.11
Sift
Uncertain
0.020
D;T
Sift4G
Benign
0.27
T;T
Polyphen
0.92
P;.
Vest4
0.13
MutPred
0.35
Loss of catalytic residue at L179 (P = 0.0449);.;
MVP
0.22
MPC
0.18
ClinPred
0.25
T
GERP RS
1.6
Varity_R
0.048
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs778869440; hg19: chr1-159802827; API