chr6-26413274-C-T

Variant names:

• chr6-26413274-C-T
• rs1762281697
• NM_007048.6:c.1124C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007048.6(BTN3A1):​c.1124C>T​(p.Pro375Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

BTN3A1 (HGNC:1138): (butyrophilin subfamily 3 member A1) 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., BNT3A1) 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]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26295847).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007048.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A1	NM_007048.6	MANE Select	c.1124C>T	p.Pro375Leu	missense	Exon 10 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.968C>T	p.Pro323Leu	missense	Exon 10 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.*744C>T		3_prime_UTR	Exon 10 of 10	NP_001138481.1	O00481-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A1	ENST00000289361.11	TSL:1 MANE Select	c.1124C>T	p.Pro375Leu	missense	Exon 10 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000850859.1		c.1124C>T	p.Pro375Leu	missense	Exon 10 of 10	ENSP00000520946.1
	BTN3A1	ENST00000865809.1		c.1124C>T	p.Pro375Leu	missense	Exon 10 of 10	ENSP00000535868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Benign	0.089
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.8
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.17
Sift	Benign	0.085	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.55		Loss of disorder (P = 0.0324)
MVP		0.48
MPC		0.097
ClinPred		0.94	D
GERP RS		3.0
Varity_R		0.24
gMVP		0.14
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs1762281697; hg19: chr6-26413502;