6-26413274-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007048.6(BTN3A1):​c.1124C>G​(p.Pro375Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P375L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30018836).

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>G	p.Pro375Arg	missense	Exon 10 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.968C>G	p.Pro323Arg	missense	Exon 10 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.*744C>G		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>G	p.Pro375Arg	missense	Exon 10 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000850859.1		c.1124C>G	p.Pro375Arg	missense	Exon 10 of 10	ENSP00000520946.1
	BTN3A1	ENST00000865809.1		c.1124C>G	p.Pro375Arg	missense	Exon 10 of 10	ENSP00000535868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.8
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.52		Loss of sheet (P = 0.0315)
MVP		0.42
MPC		0.15
ClinPred		0.93	D
GERP RS		3.0
Varity_R		0.48
gMVP		0.13
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs1762281697; hg19: chr6-26413502;