Genetic Variant NM_197975.3:c.53A>G (chr5-180992816-A-G) – 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.53A>G(p.Gln18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,462,978 control chromosomes in the GnomAD database, including 3 homozygotes. 14/22 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: 0.0000053 ( 3 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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 -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 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.53A>G	p.Gln18Arg	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.53A>G	p.Gln18Arg	missense	Exon 2 of 8	ENSP00000341787.6	Q6UXE8-1
BTNL3	ENST00000899564.1		c.53A>G	p.Gln18Arg	missense	Exon 2 of 8	ENSP00000569623.1
BTNL3	ENST00000946317.1		c.49+3739A>G		intron	N/A	ENSP00000616376.1

Frequencies

GnomAD3 genomes

AF:

0.00000733

AC:

AN:

136418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000775

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000528

AC:

AN:

1326560

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

661450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32884

American (AMR)

AF:

0.00

AC:

AN:

40408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

36372

South Asian (SAS)

AF:

0.00

AC:

AN:

84672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5126

European-Non Finnish (NFE)

AF:

0.00000700

AC:

AN:

999290

Other (OTH)

AF:

0.00

AC:

AN:

55456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000733

AC:

AN:

136418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39618

American (AMR)

AF:

0.0000775

AC:

AN:

12908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3326

East Asian (EAS)

AF:

0.00

AC:

AN:

4630

South Asian (SAS)

AF:

0.00

AC:

AN:

4586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59610

Other (OTH)

AF:

0.00

AC:

AN:

1878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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

0.093

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.011

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.29

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

PhyloP100

3.5

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.3

REVEL

Benign

0.12

Sift

Benign

0.21

Sift4G

Uncertain

0.039

Polyphen

0.98

Vest4

0.32

MutPred

0.62

Gain of solvent accessibility (P = 0.1505)

MVP

0.41

MPC

0.88

ClinPred

0.30

GERP RS

1.5

Varity_R

0.078

gMVP

0.059

Mutation Taster

=100/0

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over