5-181045589-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152547.5(BTNL9):​c.100C>T​(p.Pro34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,036 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: 0.0000014 ( 0 hom. )

Consequence

BTNL9
NM_152547.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0910
Variant links:
Genes affected
BTNL9 (HGNC:24176): (butyrophilin like 9) Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0444237).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTNL9NM_152547.5 linkc.100C>T p.Pro34Ser missense_variant Exon 2 of 11 ENST00000327705.14 NP_689760.2 Q6UXG8-1Q8N324

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTNL9ENST00000327705.14 linkc.100C>T p.Pro34Ser missense_variant Exon 2 of 11 1 NM_152547.5 ENSP00000330200.9 Q6UXG8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459036
Hom.:
0
Cov.:
32
AF XY:
0.00000276
AC XY:
2
AN XY:
725930
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
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.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 04, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.100C>T (p.P34S) alteration is located in exon 2 (coding exon 1) of the BTNL9 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the proline (P) at amino acid position 34 to be replaced by a serine (S). 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
0.078
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.95
DANN
Benign
0.76
DEOGEN2
Benign
0.015
.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.34
T;T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.044
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.15
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.010
Sift
Benign
0.50
T;T
Sift4G
Benign
0.071
T;T
Polyphen
0.0010
.;B
Vest4
0.10
MutPred
0.24
Gain of phosphorylation at P34 (P = 0.0412);Gain of phosphorylation at P34 (P = 0.0412);
MVP
0.24
MPC
0.26
ClinPred
0.065
T
GERP RS
-0.65
Varity_R
0.024
gMVP
0.089

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr5-180472589; API