Variant 5-180911564-T-C 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.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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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:

BTNL8 (HGNC:):

BTNL8 links:

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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	Protein	UniProt
BTNL8	NM_001040462.3 linkuse as main transcript	c.623T>C	p.Met208Thr	missense_variant	3/8	ENST00000340184.9	NP_001035552.1	Q6UX41-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL8	ENST00000340184.9 linkuse as main transcript	c.623T>C	p.Met208Thr	missense_variant	3/8	1	NM_001040462.3	ENSP00000342197.4		Q6UX41-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

250422

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

135328

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000132

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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

Jul 15, 2024

The c.623T>C (p.M208T) alteration is located in exon 3 (coding exon 3) of the BTNL8 gene. This alteration results from a T to C substitution at nucleotide position 623, causing the methionine (M) at amino acid position 208 to be replaced by a threonine (T). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.014

.;T;.;.;.;.;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

T;T;.;T;T;T;D;T

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.61

D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N;.;N;.;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N;N;N;N;.;N;N

REVEL

Benign

0.15

Sift

Benign

0.068

T;D;D;T;D;.;D;D

Sift4G

Uncertain

0.011

D;D;D;D;T;D;D;T

Polyphen

0.036

.;B;.;.;.;.;.;.

Vest4

0.40

MutPred

0.79

Gain of catalytic residue at M208 (P = 0.0298);Gain of catalytic residue at M208 (P = 0.0298);.;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

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