Genetic Variant NM_197975.3:c.160C>T (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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL3	NM_197975.3 link	c.160C>T	p.Arg54Trp	missense_variant	Exon 2 of 8	ENST00000342868.7	NP_932079.1	Q6UXE8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL3	ENST00000342868.7 link	c.160C>T	p.Arg54Trp	missense_variant	Exon 2 of 8	1	NM_197975.3	ENSP00000341787.6		Q6UXE8-1
ENSG00000299843	ENST00000766731.1 link	n.395-41064G>A		intron_variant	Intron 2 of 2

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.160C>T (p.R54W) alteration is located in exon 2 (coding exon 2) of the BTNL3 gene. This alteration results from a C to T substitution at nucleotide position 160, causing the arginine (R) at amino acid position 54 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over