Genetic Variant BTNL9:p.Ala200Val (chr5-181050232-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152547.5(BTNL9):c.599C>T(p.Ala200Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 ( 0 hom. )

Consequence

BTNL9
NM_152547.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.04

Variant links:

Genes affected

BTNL9 (HGNC:24176): (butyrophilin like 9) 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]

BTNL9 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05440098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL9	NM_152547.5 link	c.599C>T	p.Ala200Val	missense_variant	Exon 4 of 11	ENST00000327705.14	NP_689760.2	Q6UXG8-1Q8N324

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BTNL9	ENST00000327705.14 link	c.599C>T	p.Ala200Val	missense_variant	Exon 4 of 11	1	NM_152547.5	ENSP00000330200.9	Q6UXG8-1
BTNL9	ENST00000376841.6 link	c.599C>T	p.Ala200Val	missense_variant	Exon 4 of 11	1		ENSP00000366037.2	Q6UXG8-3
BTNL9	ENST00000515271.1 link	c.392C>T	p.Ala131Val	missense_variant	Exon 3 of 5	2		ENSP00000427345.1	B7Z4Y8
BTNL9	ENST00000491209.5 link	n.599C>T		non_coding_transcript_exon_variant	Exon 4 of 7	2		ENSP00000425424.1	Q6UXG8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251460

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.599C>T (p.A200V) alteration is located in exon 4 (coding exon 3) of the BTNL9 gene. This alteration results from a C to T substitution at nucleotide position 599, causing the alanine (A) at amino acid position 200 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

.;T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.95

L;L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.42

T;T;T

Sift4G

Uncertain

0.046

D;T;T

Polyphen

0.049, 0.95

.;B;P

Vest4

0.069

MutPred

0.42

Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);.;

MVP

0.32

MPC

0.27

ClinPred

0.23

GERP RS

0.78

Varity_R

0.044

gMVP

0.086

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