Genetic Variant BTNL3:p.Arg54Trp (chr5-180992923-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_197975.3(BTNL3):c.160C>T(p.Arg54Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,326,948 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000014 ( 2 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

Publications

3 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 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.160C>T	p.Arg54Trp	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.160C>T	p.Arg54Trp	missense	Exon 2 of 8	ENSP00000341787.6	Q6UXE8-1
BTNL3	ENST00000899564.1		c.160C>T	p.Arg54Trp	missense	Exon 2 of 8	ENSP00000569623.1
BTNL3	ENST00000946317.1		c.49+3846C>T		intron	N/A	ENSP00000616376.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000174

AC:

AN:

229436

AF XY:

0.00000801

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000958

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1326948

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

661614

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32892

American (AMR)

AF:

0.0000742

AC:

AN:

40408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

36370

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5424

European-Non Finnish (NFE)

AF:

0.00000801

AC:

AN:

999334

Other (OTH)

AF:

0.0000361

AC:

AN:

55478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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

Cov.:

ExAC

AF:

0.00000883

AC:

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

0.22

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

2.9

PhyloP100

0.090

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.50

MutPred

0.69

Loss of methylation at R54 (P = 0.0393)

MVP

0.67

MPC

0.86

ClinPred

0.95

GERP RS

-1.5

Varity_R

0.29

gMVP

0.50

Mutation Taster

=96/4

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