Genetic Variant BTNL8:p.Met208Thr (chr5-180911564-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001040462.3(BTNL8):c.623T>C(p.Met208Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000164 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BTNL8
NM_001040462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040462.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL8	NM_001040462.3	MANE Select	c.623T>C	p.Met208Thr	missense	Exon 3 of 8	NP_001035552.1	Q6UX41-1
BTNL8	NM_001159707.2		c.275T>C	p.Met92Thr	missense	Exon 2 of 7	NP_001153179.1	Q6UX41-6
BTNL8	NM_001159709.2		c.248T>C	p.Met83Thr	missense	Exon 3 of 8	NP_001153181.1	Q6UX41-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.623T>C	p.Met208Thr	missense	Exon 3 of 8	ENSP00000342197.4	Q6UX41-1
BTNL8	ENST00000511704.5	TSL:1	c.275T>C	p.Met92Thr	missense	Exon 2 of 7	ENSP00000425207.1	Q6UX41-6
BTNL8	ENST00000231229.8	TSL:1	c.623T>C	p.Met208Thr	missense	Exon 3 of 8	ENSP00000231229.4	Q6UX41-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000399

AC:

AN:

250422

AF XY:

0.0000665

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111986

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.000132

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Uncertain

0.42

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.014

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

PhyloP100

4.3

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Benign

0.068

Sift4G

Uncertain

0.011

Polyphen

0.036

Vest4

0.40

MutPred

0.79

Gain of catalytic residue at M208 (P = 0.0298)

MVP

0.59

MPC

0.16

ClinPred

0.078

GERP RS

3.7

Varity_R

0.68

gMVP

0.19

Mutation Taster

=154/46

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