Variant 5-180950080-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040462.3(BTNL8):c.1039G>A(p.Gly347Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,463,000 control chromosomes in the GnomAD database, including 1 homozygotes. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000045 ( 1 hom. )

Consequence

BTNL8
NM_001040462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

Variant links:

Genes affected

BTNL8 (HGNC:26131): (butyrophilin like 8) 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 located in plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

BTNL8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL8	NM_001040462.3 linkuse as main transcript	c.1039G>A	p.Gly347Arg	missense_variant	8/8	ENST00000340184.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL8	ENST00000340184.9 linkuse as main transcript	c.1039G>A	p.Gly347Arg	missense_variant	8/8	1	NM_001040462.3	P1	Q6UX41-1

Frequencies

GnomAD3 genomes

AF:

0.0000147

AC:

AN:

135874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000507

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

230128

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000957

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000452

AC:

AN:

1327126

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

AN XY:

661718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000742

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000100

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

AF:

0.0000147

AC:

AN:

135874

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

65918

show subpopulations

Gnomad4 AFR

AF:

0.0000507

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000176

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.1039G>A (p.G347R) alteration is located in exon 8 (coding exon 8) of the BTNL8 gene. This alteration results from a G to A substitution at nucleotide position 1039, causing the glycine (G) at amino acid position 347 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;.;.;.;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.59

T;.;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.60

D;D;D;D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

N;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.25

N;N;N;.;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0060

D;D;D;.;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D;D

Polyphen

0.89

P;.;.;.;.;.

Vest4

0.29

MutPred

0.79

Gain of MoRF binding (P = 0.0155);.;.;.;.;.;

MVP

0.63

MPC

0.44

ClinPred

0.76

GERP RS

0.97

Varity_R

0.070

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over