6-26445754-A-T

Position:

• chr6-26445754-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006994.5(BTN3A3):​c.484A>T​(p.Ile162Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN3A3 NM_006994.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

Genes affected

BTN3A3 (HGNC:1140): (butyrophilin subfamily 3 member A3) The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A3) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

BTN3A3 (HGNC:):

ACMG classification

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=0.30851492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.484A>T	p.Ile162Phe	missense_variant	5/11	ENST00000244519.7	NP_008925.1
BTN3A3	NM_197974.3	c.358A>T	p.Ile120Phe	missense_variant	5/10		NP_932078.2
BTN3A3	NM_001242803.2	c.307+1450A>T		intron_variant			NP_001229732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN3A3	ENST00000244519.7	c.484A>T	p.Ile162Phe	missense_variant	5/11	1	NM_006994.5	ENSP00000244519.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Mar 15, 2024

The c.484A>T (p.I162F) alteration is located in exon 5 (coding exon 3) of the BTN3A3 gene. This alteration results from a A to T substitution at nucleotide position 484, causing the isoleucine (I) at amino acid position 162 to be replaced by a phenylalanine (F). 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	0.24
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;.;.;.
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Benign	0.064
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.56
MutPred		0.62		Loss of sheet (P = 0.1158);.;.;Loss of sheet (P = 0.1158);.;
MVP		0.39
MPC		0.31
ClinPred		0.99	D
GERP RS		1.8
Varity_R		0.45
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1581653535; hg19: chr6-26445982;