Genetic Variant BTNL3:p.Glu124Ala (chr5-180993134-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_197975.3(BTNL3):c.371A>C(p.Glu124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,444,390 control chromosomes in the GnomAD database, including 8 homozygotes. 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 0.0000073 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000024 ( 8 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.297

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18339676).

BS2

High Homozygotes in GnomAdExome4 at 8 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.371A>C	p.Glu124Ala	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.371A>C	p.Glu124Ala	missense	Exon 2 of 8	ENSP00000341787.6	Q6UXE8-1
BTNL3	ENST00000899564.1		c.371A>C	p.Glu124Ala	missense	Exon 2 of 8	ENSP00000569623.1
BTNL3	ENST00000946317.1		c.49+4057A>C		intron	N/A	ENSP00000616376.1

Frequencies

GnomAD3 genomes

AF:

0.00000731

AC:

AN:

136736

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

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

194508

AF XY:

0.0000190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.000221

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:

0.0000245

AC:

AN:

1307654

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

649970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32616

American (AMR)

AF:

0.0000804

AC:

AN:

37312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24788

East Asian (EAS)

AF:

0.00

AC:

AN:

35474

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45918

Middle Eastern (MID)

AF:

0.00131

AC:

AN:

5338

European-Non Finnish (NFE)

AF:

0.0000121

AC:

AN:

988968

Other (OTH)

AF:

0.000164

AC:

AN:

54834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000731

AC:

AN:

136736

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

66464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39738

American (AMR)

AF:

0.00

AC:

AN:

12928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3332

East Asian (EAS)

AF:

0.00

AC:

AN:

4680

South Asian (SAS)

AF:

0.00

AC:

AN:

4582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

59692

Other (OTH)

AF:

0.00

AC:

AN:

1890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000180

AC:

Asia WGS

AF:

0.000302

AC:

AN:

3326

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

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.50

M_CAP

Benign

0.0094

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

PhyloP100

0.30

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.064

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.018

Polyphen

0.58

Vest4

0.32

MutPred

0.58

Loss of disorder (P = 0.1386)

MVP

0.37

MPC

1.0

ClinPred

0.38

GERP RS

1.6

Varity_R

0.13

gMVP

0.24

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over