5-180911425-C-G

Position:

• chr5-180911425-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040462.3(BTNL8):​c.484C>G​(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: BTNL8 NM_001040462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.10

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08379638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTNL8	NM_001040462.3	c.484C>G	p.Arg162Gly	missense_variant	3/8	ENST00000340184.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTNL8	ENST00000340184.9	c.484C>G	p.Arg162Gly	missense_variant	3/8	1	NM_001040462.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.484C>G (p.R162G) alteration is located in exon 3 (coding exon 3) of the BTNL8 gene. This alteration results from a C to G substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.6
DANN	Benign	0.91
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.43	T;T;.;T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.084	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D;.
REVEL	Benign	0.069
Sift	Uncertain	0.0030	D;D;D;D;D;.
Sift4G	Uncertain	0.010	D;D;T;D;D;T
Polyphen		0.17	.;B;.;.;.;.
Vest4		0.17
MutPred		0.47		Gain of ubiquitination at K166 (P = 0.0418);Gain of ubiquitination at K166 (P = 0.0418);.;Gain of ubiquitination at K166 (P = 0.0418);.;.;
MVP		0.13
MPC		0.21
ClinPred		0.18	T
GERP RS		-7.7
Varity_R		0.082
gMVP		0.098

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-180338425;