Genetic Variant BTNL3:p.Thr46Ile (chr5-180992900-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_197975.3(BTNL3):c.137C>T(p.Thr46Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,463,158 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000014 ( 6 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.17

Publications

0 publications found

Variant links:

Genes affected

BTNL3 (HGNC:1143): (butyrophilin like 3) Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be integral component of membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

BTNL3 links:

ENSG00000299843 (HGNC:):

ENSG00000299843 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060624868).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197975.3. 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
	BTNL3	NM_197975.3	MANE Select	c.137C>T	p.Thr46Ile	missense	Exon 2 of 8	NP_932079.1	Q6UXE8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL3	ENST00000342868.7	TSL:1 MANE Select	c.137C>T	p.Thr46Ile	missense	Exon 2 of 8	ENSP00000341787.6	Q6UXE8-1
BTNL3	ENST00000899564.1		c.137C>T	p.Thr46Ile	missense	Exon 2 of 8	ENSP00000569623.1
BTNL3	ENST00000946317.1		c.49+3823C>T		intron	N/A	ENSP00000616376.1

Frequencies

GnomAD3 genomes

AF:

0.00000735

AC:

AN:

136142

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000168

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1327016

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

661650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32894

American (AMR)

AF:

0.00

AC:

AN:

40414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25136

East Asian (EAS)

AF:

0.00

AC:

AN:

36372

South Asian (SAS)

AF:

0.00

AC:

AN:

84688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5424

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

999370

Other (OTH)

AF:

0.00

AC:

AN:

55476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00000735

AC:

AN:

136142

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

66104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39522

American (AMR)

AF:

0.00

AC:

AN:

12820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3304

East Asian (EAS)

AF:

0.00

AC:

AN:

4620

South Asian (SAS)

AF:

0.00

AC:

AN:

4602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8740

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

59586

Other (OTH)

AF:

0.00

AC:

AN:

1878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.7

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0016

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.56

M_CAP

Benign

0.043

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.24

PhyloP100

-1.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.0

REVEL

Benign

0.011

Sift

Benign

0.41

Sift4G

Benign

0.47

Polyphen

0.061

Vest4

0.14

MutPred

0.47

Loss of disorder (P = 0.0503)

MVP

0.061

MPC

0.85

ClinPred

0.056

GERP RS

-4.1

Varity_R

0.028

gMVP

0.12

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over