Genetic Variant BTNL8:p.Pro79Ser (chr5-180908771-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040462.3(BTNL8):c.235C>T(p.Pro79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 6.8e-7 ( 0 hom. )

Consequence

BTNL8
NM_001040462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.546

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15336275).

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.235C>T	p.Pro79Ser	missense	Exon 2 of 8	NP_001035552.1	Q6UX41-1
BTNL8	NM_024850.3		c.235C>T	p.Pro79Ser	missense	Exon 2 of 8	NP_079126.1	Q6UX41-5
BTNL8	NM_001159708.2		c.235C>T	p.Pro79Ser	missense	Exon 2 of 7	NP_001153180.1	Q6UX41-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.235C>T	p.Pro79Ser	missense	Exon 2 of 8	ENSP00000342197.4	Q6UX41-1
BTNL8	ENST00000231229.8	TSL:1	c.235C>T	p.Pro79Ser	missense	Exon 2 of 8	ENSP00000231229.4	Q6UX41-5
BTNL8	ENST00000508408.5	TSL:1	c.235C>T	p.Pro79Ser	missense	Exon 2 of 7	ENSP00000424585.1	Q6UX41-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

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:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

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

GnomAD4 genome

Cov.:

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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.42

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.8

PhyloP100

-0.55

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.13

Sift

Benign

0.24

Sift4G

Benign

0.19

Polyphen

0.97

Vest4

0.17

MutPred

0.42

Loss of catalytic residue at P79 (P = 0.031)

MVP

0.78

MPC

0.29

ClinPred

0.66

GERP RS

-0.93

Varity_R

0.036

gMVP

0.045

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over