chr6-26413477-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_007048.6(BTN3A1):c.1327A>G(p.Thr443Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

BTN3A1
NM_007048.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.223

Publications

0 publications found

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:

ENSG00000291336 (HGNC:):

ENSG00000291336 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019874007).

BP6

Variant 6-26413477-A-G is Benign according to our data. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-26413477-A-G is described in CliVar as Likely_benign. Clinvar id is 2378386.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN3A1	NM_007048.6 link	c.1327A>G	p.Thr443Ala	missense_variant	Exon 10 of 10	ENST00000289361.11	NP_008979.3	O00481-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN3A1	ENST00000289361.11 link	c.1327A>G	p.Thr443Ala	missense_variant	Exon 10 of 10	1	NM_007048.6	ENSP00000289361.6		O00481-1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151952

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:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000127

AC:

AN:

251486

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000108

AC:

158

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000336

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000890

AC:

AN:

1112010

Other (OTH)

AF:

0.000248

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000900

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

May 26, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.032

(source)

DANN

Benign

0.097

DEOGEN2

Benign

0.0024

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.15

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.2

N;.

PhyloP100

-0.22

PrimateAI

Benign

0.28

PROVEAN

Benign

2.3

N;N

REVEL

Benign

0.059

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.0090

MutPred

0.44

Loss of phosphorylation at T443 (P = 0.0447);.;

MVP

0.23

MPC

0.056

ClinPred

0.018

GERP RS

-0.65

Varity_R

0.094

gMVP

0.057

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over