5-181050232-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.599C>T​(p.Ala200Val) 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 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.04
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]

Genome browser will be placed here

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=0.05440098).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTNL9NM_152547.5 linkc.599C>T p.Ala200Val missense_variant Exon 4 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.599C>T p.Ala200Val missense_variant Exon 4 of 11 1 NM_152547.5 ENSP00000330200.9 Q6UXG8-1
BTNL9ENST00000376841.6 linkc.599C>T p.Ala200Val missense_variant Exon 4 of 11 1 ENSP00000366037.2 Q6UXG8-3
BTNL9ENST00000515271.1 linkc.392C>T p.Ala131Val missense_variant Exon 3 of 5 2 ENSP00000427345.1 B7Z4Y8
BTNL9ENST00000491209.5 linkn.599C>T non_coding_transcript_exon_variant Exon 4 of 7 2 ENSP00000425424.1 Q6UXG8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251460
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461810
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727186
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0
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
Jan 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.599C>T (p.A200V) alteration is located in exon 4 (coding exon 3) of the BTNL9 gene. This alteration results from a C to T substitution at nucleotide position 599, causing the alanine (A) at amino acid position 200 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
3.5
DANN
Uncertain
0.99
DEOGEN2
Benign
0.053
.;T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.054
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.95
L;L;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.031
Sift
Benign
0.42
T;T;T
Sift4G
Uncertain
0.046
D;T;T
Polyphen
0.049, 0.95
.;B;P
Vest4
0.069
MutPred
0.42
Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);.;
MVP
0.32
MPC
0.27
ClinPred
0.23
T
GERP RS
0.78
Varity_R
0.044
gMVP
0.086

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: rs746263568; hg19: chr5-180477232; COSMIC: COSV99047466; COSMIC: COSV99047466; API