6-26368645-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007047.5(BTN3A2):ā€‹c.166C>Gā€‹(p.Pro56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 31)
Exomes š‘“: 0.00015 ( 0 hom. )

Consequence

BTN3A2
NM_007047.5 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46
Variant links:
Genes affected
BTN3A2 (HGNC:1139): (butyrophilin subfamily 3 member A2) This gene encodes a member of the immunoglobulin superfamily, which resides in the juxta-telomeric region of the major histocompatability class 1 locus and is clustered with the other family members on chromosome 6. The encoded protein may be involved in the adaptive immune response. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3340407).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BTN3A2NM_007047.5 linkuse as main transcriptc.166C>G p.Pro56Ala missense_variant 4/11 ENST00000377708.7 NP_008978.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BTN3A2ENST00000377708.7 linkuse as main transcriptc.166C>G p.Pro56Ala missense_variant 4/111 NM_007047.5 ENSP00000366937 P2P78410-1
ENST00000707189.1 linkuse as main transcriptn.1000-184542C>G intron_variant, non_coding_transcript_variant
ENST00000707191.1 linkuse as main transcriptn.1001-164060C>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152266
Hom.:
0
Cov.:
31
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251170
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135738
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:
0.0000705
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000146
AC:
213
AN:
1461668
Hom.:
0
Cov.:
31
AF XY:
0.000128
AC XY:
93
AN XY:
727146
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:
0.000188
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152266
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 02, 2023The c.166C>G (p.P56A) alteration is located in exon 4 (coding exon 2) of the BTN3A2 gene. This alteration results from a C to G substitution at nucleotide position 166, causing the proline (P) at amino acid position 56 to be replaced by an alanine (A). 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
Uncertain
0.48
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.17
.;.;.;.;.;T;T;T;T
Eigen
Benign
-0.059
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.076
N
LIST_S2
Uncertain
0.97
D;D;D;D;D;.;.;.;D
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.33
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.0
.;.;.;.;.;M;M;M;M
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.45
T
PROVEAN
Pathogenic
-7.5
D;D;D;D;D;D;D;D;D
REVEL
Benign
0.025
Sift
Uncertain
0.0020
D;D;D;D;D;D;D;D;D
Sift4G
Benign
0.066
T;T;T;D;D;T;T;T;T
Polyphen
1.0
.;.;.;.;.;D;D;D;D
Vest4
0.35, 0.34, 0.35, 0.35, 0.33, 0.35
MVP
0.62
MPC
3.3
ClinPred
0.79
D
GERP RS
2.3
Varity_R
0.45
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs758725669; hg19: chr6-26368873; API