NM_007048.6:c.788T>C

Variant names:

• chr6-26409605-T-C
• rs754940106
• NM_007048.6:c.788T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007048.6(BTN3A1):​c.788T>C​(p.Leu263Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,612,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18539253).

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.788T>C	p.Leu263Pro	missense	Exon 5 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.632T>C	p.Leu211Pro	missense	Exon 5 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.788T>C	p.Leu263Pro	missense	Exon 5 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.788T>C	p.Leu263Pro	missense	Exon 5 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.788T>C	p.Leu263Pro	missense	Exon 5 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.788T>C	p.Leu263Pro	missense	Exon 5 of 10	ENSP00000520946.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 151980 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 249358 AF XY: 0.000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000720

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000797

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 181 AN: 1460528 Hom.: 0 Cov.: 32 AF XY: 0.000120 AC XY: 87 AN XY: 726756

African (AFR) AF: 0.00 AC: 0 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 44144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.000932 AC: 37 AN: 39688

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86226

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000114 AC: 127 AN: 1111654

Other (OTH) AF: 0.0000663 AC: 4 AN: 60302

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 151980 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74220

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000197 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.27
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.081	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.9
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.64		Loss of stability (P = 0.0258)
MVP		0.56
MPC		0.45
ClinPred		0.25	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.71
gMVP		0.23
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: rs754940106; hg19: chr6-26409833; COSMIC: COSV99175640; COSMIC: COSV99175640;