5-180992923-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_197975.3(BTNL3):​c.160C>G​(p.Arg54Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,463,046 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R54P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0000023 ( 1 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0900

Publications

3 publications found
Variant links:
Genes affected
BTNL3 (HGNC:1143): (butyrophilin like 3) 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 integral component of 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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTNL3NM_197975.3 linkc.160C>G p.Arg54Gly missense_variant Exon 2 of 8 ENST00000342868.7 NP_932079.1 Q6UXE8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTNL3ENST00000342868.7 linkc.160C>G p.Arg54Gly missense_variant Exon 2 of 8 1 NM_197975.3 ENSP00000341787.6 Q6UXE8-1
ENSG00000299843ENST00000766731.1 linkn.395-41064G>C intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.0000147
AC:
2
AN:
136098
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000228
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000436
AC:
1
AN:
229436
AF XY:
0.00
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 FIN exome
AF:
0.0000524
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000226
AC:
3
AN:
1326948
Hom.:
1
Cov.:
31
AF XY:
0.00000302
AC XY:
2
AN XY:
661614
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32892
American (AMR)
AF:
0.00
AC:
0
AN:
40408
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36370
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84676
European-Finnish (FIN)
AF:
0.0000635
AC:
3
AN:
47236
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5424
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
999334
Other (OTH)
AF:
0.00
AC:
0
AN:
55478
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000147
AC:
2
AN:
136098
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
66136
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
39484
American (AMR)
AF:
0.00
AC:
0
AN:
12786
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3308
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4634
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4594
European-Finnish (FIN)
AF:
0.000228
AC:
2
AN:
8754
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
302
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
59578
Other (OTH)
AF:
0.00
AC:
0
AN:
1884
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000883
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
14
DANN
Benign
0.95
DEOGEN2
Benign
0.081
T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.65
T
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.3
M
PhyloP100
0.090
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-6.0
D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.80
P
Vest4
0.53
MutPred
0.71
Loss of methylation at R54 (P = 0.0393);
MVP
0.55
MPC
1.3
ClinPred
0.98
D
GERP RS
-1.5
Varity_R
0.32
gMVP
0.62
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs780363306; hg19: chr5-180419923; API