5-180899323-C-T

Variant names:

• chr5-180899323-C-T
• rs1756725085
• NM_001040462.3:c.13C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040462.3(BTNL8):​c.13C>T​(p.Leu5Phe) 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. 15/22 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)
• Consequence: BTNL8 NM_001040462.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.433
• Publications: 0 publications found

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

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=0.070485175).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL8	NM_001040462.3	MANE Select	c.13C>T	p.Leu5Phe	missense	Exon 1 of 8	NP_001035552.1	Q6UX41-1
	BTNL8	NM_001159707.2		c.13C>T	p.Leu5Phe	missense	Exon 1 of 7	NP_001153179.1	Q6UX41-6
	BTNL8	NM_024850.3		c.13C>T	p.Leu5Phe	missense	Exon 1 of 8	NP_079126.1	Q6UX41-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.13C>T	p.Leu5Phe	missense	Exon 1 of 8	ENSP00000342197.4	Q6UX41-1
	BTNL8	ENST00000511704.5	TSL:1	c.13C>T	p.Leu5Phe	missense	Exon 1 of 7	ENSP00000425207.1	Q6UX41-6
	BTNL8	ENST00000231229.8	TSL:1	c.13C>T	p.Leu5Phe	missense	Exon 1 of 8	ENSP00000231229.4	Q6UX41-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.7
DANN	Benign	0.77
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.43
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.0070
Sift	Benign	0.69	T
Sift4G	Uncertain	0.026	D
Polyphen		0.33	B
Vest4		0.10
MutPred		0.43		Loss of disorder (P = 0.1081)
MVP		0.40
MPC		0.15
ClinPred		0.14	T
GERP RS		-1.1
PromoterAI		0.028	Neutral
Varity_R		0.076
gMVP		0.071
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1756725085; hg19: chr5-180326323;