6-26407828-C-G

Variant names:

• chr6-26407828-C-G
• rs200236658
• NM_007048.6:c.591C>G

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.591C>G​(p.Asp197Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• 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=0.18224248).

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.591C>G	p.Asp197Glu	missense	Exon 4 of 10	NP_008979.3
	BTN3A1	NM_001145009.2		c.591C>G	p.Asp197Glu	missense	Exon 4 of 10	NP_001138481.1	O00481-3
	BTN3A1	NM_194441.3		c.591C>G	p.Asp197Glu	missense	Exon 4 of 10	NP_919423.1	O00481-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A1	ENST00000289361.11	TSL:1 MANE Select	c.591C>G	p.Asp197Glu	missense	Exon 4 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.591C>G	p.Asp197Glu	missense	Exon 4 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.591C>G	p.Asp197Glu	missense	Exon 4 of 10	ENSP00000520946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.5
DANN	Benign	0.91
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.86	T
PhyloP100		-3.2
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.089
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.074	T
Polyphen		1.0	D
Vest4		0.084
MutPred		0.64		Gain of loop (P = 0.2045)
MVP		0.40
MPC		0.36
ClinPred		0.45	T
GERP RS		-4.0
Varity_R		0.19
gMVP		0.063
Mutation Taster		=97/3	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: rs200236658; hg19: chr6-26408056;