5-180911573-C-T

Position:

• chr5-180911573-C-T

Variant summary

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

The NM_001040462.3(BTNL8):​c.632C>T​(p.Ala211Val) 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. 15/21 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: 0.214

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=0.09388438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL8	NM_001040462.3	c.632C>T	p.Ala211Val	missense_variant	3/8	ENST00000340184.9	NP_001035552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL8	ENST00000340184.9	c.632C>T	p.Ala211Val	missense_variant	3/8	1	NM_001040462.3	ENSP00000342197.4

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

Aug 19, 2024

The c.632C>T (p.A211V) alteration is located in exon 3 (coding exon 3) of the BTNL8 gene. This alteration results from a C to T substitution at nucleotide position 632, causing the alanine (A) at amino acid position 211 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	0.097
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.4
DANN	Benign	0.57
DEOGEN2	Benign	0.0026	.;T;.;.;.;.;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.70	T;T;.;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.094	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.;L;.;.;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.62	N;N;N;N;N;.;N;N
REVEL	Benign	0.041
Sift	Benign	0.19	T;T;T;T;T;.;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T;T
Polyphen		0.060	.;B;.;.;.;.;.;.
Vest4		0.12
MutPred		0.27		Loss of disorder (P = 0.0781);Loss of disorder (P = 0.0781);.;Loss of disorder (P = 0.0781);.;.;.;.;
MVP		0.70
MPC		0.14
ClinPred		0.069	T
GERP RS		1.4
Varity_R		0.034
gMVP		0.037

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: chr5-180338573;