chr6-26406124-C-T

Variant names:

• chr6-26406124-C-T
• rs926171888
• NM_007048.6:c.301C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_007048.6(BTN3A1):​c.301C>T​(p.Arg101Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,569,624 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 22)
  • Exomes 𝑓: 0.000023 (1 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.874
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33598775).

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.301C>T	p.Arg101Trp	missense	Exon 3 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.301C>T	p.Arg101Trp	missense	Exon 3 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.301C>T	p.Arg101Trp	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.301C>T	p.Arg101Trp	missense	Exon 3 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.301C>T	p.Arg101Trp	missense	Exon 3 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.301C>T	p.Arg101Trp	missense	Exon 3 of 10	ENSP00000520946.1

Frequencies

GnomAD3 genomes AF: 0.0000207 AC: 3 AN: 145252 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000299

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000266 AC: 5 AN: 187684 AF XY: 0.00000986

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000712

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000255

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000232 AC: 33 AN: 1424372 Hom.: 1 Cov.: 31 AF XY: 0.0000226 AC XY: 16 AN XY: 708686

African (AFR) AF: 0.0000323 AC: 1 AN: 30930

American (AMR) AF: 0.000115 AC: 5 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.0000780 AC: 2 AN: 25654

East Asian (EAS) AF: 0.000330 AC: 13 AN: 39448

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 0.00000922 AC: 10 AN: 1084510

Other (OTH) AF: 0.00 AC: 0 AN: 59046

GnomAD4 genome AF: 0.0000207 AC: 3 AN: 145252 Hom.: 0 Cov.: 22 AF XY: 0.0000142 AC XY: 1 AN XY: 70496

African (AFR) AF: 0.00 AC: 0 AN: 37598

American (AMR) AF: 0.00 AC: 0 AN: 14576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9894

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

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66968

Other (OTH) AF: 0.00 AC: 0 AN: 1974

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000113

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	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.016	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		-0.87
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.50		Loss of disorder (P = 0.0365)
MVP		0.75
MPC		3.4
ClinPred		0.99	D
GERP RS		-2.8
Varity_R		0.21
gMVP		0.28
Mutation Taster		=84/16	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: rs926171888; hg19: chr6-26406352; COSMIC: COSV99175644; COSMIC: COSV99175644;