Variant chr6-26406124-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

BTN3A1
NM_007048.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.874

Variant links:

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]

BTN3A1 links:

BTN3A1 (HGNC:):

BTN3A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN3A1	NM_007048.6 linkuse as main transcript	c.301C>T	p.Arg101Trp	missense_variant	3/10	ENST00000289361.11	NP_008979.3	O00481-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN3A1	ENST00000289361.11 linkuse as main transcript	c.301C>T	p.Arg101Trp	missense_variant	3/10	1	NM_007048.6	ENSP00000289361.6		O00481-1

Frequencies

GnomAD3 genomes

AF:

0.0000207

AC:

AN:

145252

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000266

AC:

AN:

187684

Hom.:

AF XY:

0.00000986

AC XY:

AN XY:

101398

show subpopulations

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 SAS exome

AF:

0.0000399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000255

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000232

AC:

AN:

1424372

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

708686

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.0000780

Gnomad4 EAS exome

AF:

0.000330

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000922

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000207

AC:

AN:

145252

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000299

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.301C>T (p.R101W) alteration is located in exon 3 (coding exon 2) of the BTN3A1 gene. This alteration results from a C to T substitution at nucleotide position 301, causing the arginine (R) at amino acid position 101 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

.;T;.;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.016

LIST_S2

Pathogenic

0.98

D;D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.34

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.3

M;M;.;M;M

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.3

D;D;D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

1.0

D;D;.;D;.

Vest4

0.22

MutPred

0.50

Loss of disorder (P = 0.0365);Loss of disorder (P = 0.0365);Loss of disorder (P = 0.0365);Loss of disorder (P = 0.0365);Loss of disorder (P = 0.0365);

MVP

0.75

MPC

3.4

ClinPred

0.99

GERP RS

-2.8

Varity_R

0.21

gMVP

0.28

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over