chr6-26406206-T-C

Variant names:

• chr6-26406206-T-C
• rs1461205077
• NM_007048.6:c.383T>C

Variant summary

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

The NM_007048.6(BTN3A1):​c.383T>C​(p.Phe128Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,430,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 24)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.383T>C	p.Phe128Ser	missense	Exon 3 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.383T>C	p.Phe128Ser	missense	Exon 3 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.383T>C	p.Phe128Ser	missense	Exon 3 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.383T>C	p.Phe128Ser	missense	Exon 3 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.383T>C	p.Phe128Ser	missense	Exon 3 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.383T>C	p.Phe128Ser	missense	Exon 3 of 10	ENSP00000520946.1

Frequencies

GnomAD3 genomes AF: 0.0000140 AC: 2 AN: 142632 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.77e-7 AC: 1 AN: 1287734 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 639762

African (AFR) AF: 0.00 AC: 0 AN: 24628

American (AMR) AF: 0.00 AC: 0 AN: 36534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23846

East Asian (EAS) AF: 0.00 AC: 0 AN: 37838

South Asian (SAS) AF: 0.00 AC: 0 AN: 77230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3832

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 981884

Other (OTH) AF: 0.00 AC: 0 AN: 54280

GnomAD4 genome AF: 0.0000140 AC: 2 AN: 142632 Hom.: 0 Cov.: 24 AF XY: 0.0000145 AC XY: 1 AN XY: 68966

African (AFR) AF: 0.0000547 AC: 2 AN: 36562

American (AMR) AF: 0.00 AC: 0 AN: 14278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66140

Other (OTH) AF: 0.00 AC: 0 AN: 1896

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0020	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.78		Gain of disorder (P = 0.0218)
MVP		0.54
MPC		5.0
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.79
gMVP		0.49
Mutation Taster		=85/15	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: rs1461205077; hg19: chr6-26406434;