6-26368760-G-A

Position:

• chr6-26368760-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007047.5(BTN3A2):​c.281G>A​(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BTN3A2 NM_007047.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

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]

(HGNC:):

ACMG classification

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=0.17180401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN3A2	NM_007047.5	c.281G>A	p.Arg94Gln	missense_variant	4/11	ENST00000377708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A2	ENST00000377708.7	c.281G>A	p.Arg94Gln	missense_variant	4/11	1	NM_007047.5	P2
	ENST00000707189.1	n.1000-184427G>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-163945G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.0000162 AC: 4 AN: 246582 Hom.: 0 AF XY: 0.0000225 AC XY: 3 AN XY: 133230

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: 0.0000360

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000171 AC: 25 AN: 1460154 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 726410

Gnomad4 AFR exome AF: 0.0000897

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: 0.0000189

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.9
DANN	Benign	0.93
DEOGEN2	Benign	0.0067	.;.;.;.;.;T;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.84	T;T;T;T;T;.;.;.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	.;.;.;.;.;L;L;L;L
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.10	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.51	T;T;T;T;T;T;T;T;T
Polyphen		0.97	.;.;.;.;.;D;D;D;D
Vest4		0.095, 0.091, 0.096, 0.085
MutPred		0.52		.;.;.;.;Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);
MVP		0.32
MPC		2.1
ClinPred		0.089	T
GERP RS		-6.3
Varity_R		0.053
gMVP		0.083

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

Other links and lift over

dbSNP: rs746878122; hg19: chr6-26368988;