Variant 6-26370439-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007047.5(BTN3A2):c.551G>A(p.Gly184Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

BTN3A2
NM_007047.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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]

BTN3A2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN3A2	NM_007047.5 linkuse as main transcript	c.551G>A	p.Gly184Glu	missense_variant	5/11	ENST00000377708.7	NP_008978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN3A2	ENST00000377708.7 linkuse as main transcript	c.551G>A	p.Gly184Glu	missense_variant	5/11	1	NM_007047.5	ENSP00000366937	P2	P78410-1
	ENST00000707189.1 linkuse as main transcript	n.1000-182748G>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1001-162266G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251476

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

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:

0.00000616

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

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 submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.551G>A (p.G184E) alteration is located in exon 5 (coding exon 3) of the BTN3A2 gene. This alteration results from a G to A substitution at nucleotide position 551, causing the glycine (G) at amino acid position 184 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;.;.;T;T;T;T

Eigen

Benign

0.059

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.81

T;T;T;.;.;.;T

M_CAP

Benign

0.0048

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;.;.;M;M;M;M

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.6

D;D;D;D;D;D;D

REVEL

Benign

0.077

Sift

Uncertain

0.020

D;D;D;D;D;D;D

Sift4G

Benign

0.34

T;T;D;D;D;D;D

Polyphen

1.0

.;.;.;D;D;D;D

Vest4

0.28, 0.28, 0.28, 0.29, 0.28

MutPred

0.71

.;.;.;Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);

MVP

0.36

MPC

0.52

ClinPred

0.53

GERP RS

2.3

Varity_R

0.24

gMVP

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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