6-26368841-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.362G>A(p.Ser121Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.9e-7 (0 hom.)
• Consequence: BTN3A2 NM_007047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.262

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=0.16338438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN3A2	NM_007047.5	c.362G>A	p.Ser121Asn	missense_variant	4/11	ENST00000377708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A2	ENST00000377708.7	c.362G>A	p.Ser121Asn	missense_variant	4/11	1	NM_007047.5	P2
	ENST00000707189.1	n.1000-184346G>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-163864G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454610 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723324

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.362G>A (p.S121N) 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 362, causing the serine (S) at amino acid position 121 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	12
Dann	Benign	0.92
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.67	T;T;T;T;T;.;.;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
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	0.15
Sift	Benign	1.0	T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T
Polyphen		0.98	.;.;.;.;.;D;D;D;D
Vest4		0.20, 0.20, 0.20, 0.20, 0.18, 0.20
MutPred		0.36		.;.;.;.;Loss of ubiquitination at K123 (P = 0.0828);Loss of ubiquitination at K123 (P = 0.0828);Loss of ubiquitination at K123 (P = 0.0828);Loss of ubiquitination at K123 (P = 0.0828);Loss of ubiquitination at K123 (P = 0.0828);
MVP		0.55
MPC		2.0
ClinPred		0.12	T
GERP RS		-2.8
Varity_R		0.055
gMVP		0.032

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-26369069;