Variant chr6-26368735-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007047.5(BTN3A2):c.256G>A(p.Glu86Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,294 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: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BTN3A2
NM_007047.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08687818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN3A2	NM_007047.5 linkuse as main transcript	c.256G>A	p.Glu86Lys	missense_variant	4/11	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.256G>A	p.Glu86Lys	missense_variant	4/11	1	NM_007047.5	ENSP00000366937	P2	P78410-1
	ENST00000707189.1 linkuse as main transcript	n.1000-184452G>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1001-163970G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461388

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000240

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Apr 04, 2024

The c.256G>A (p.E86K) alteration is located in exon 4 (coding exon 2) of the BTN3A2 gene. This alteration results from a G to A substitution at nucleotide position 256, causing the glutamic acid (E) at amino acid position 86 to be replaced by a lysine (K). 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

0.093

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0014

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

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.031

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.017

MetaRNN

Benign

0.087

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;.;.;.;.;L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.96

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.70

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

Sift4G

Benign

0.62

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

Polyphen

1.0

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

Vest4

0.15, 0.15, 0.14, 0.18, 0.15

MutPred

0.42

.;.;.;.;Gain of methylation at E86 (P = 0.0054);Gain of methylation at E86 (P = 0.0054);Gain of methylation at E86 (P = 0.0054);Gain of methylation at E86 (P = 0.0054);Gain of methylation at E86 (P = 0.0054);

MVP

0.60

MPC

3.5

ClinPred

0.79

GERP RS

-0.20

Varity_R

0.11

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over