chr5-181002698-C-T

Variant names:

• chr5-181002698-C-T
• rs1760145027
• NM_197975.3:c.700C>T

Variant summary

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

The NM_197975.3(BTNL3):​c.700C>T​(p.Arg234Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,323,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 21)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: BTNL3 NM_197975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56
• Publications: 0 publications found

Genes affected

BTNL3 (HGNC:1143): (butyrophilin like 3) 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 integral component of membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299843 (HGNC:):

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=0.14379364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197975.3. 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
	BTNL3	NM_197975.3	MANE Select	c.700C>T	p.Arg234Cys	missense	Exon 4 of 8	NP_932079.1	Q6UXE8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL3	ENST00000342868.7	TSL:1 MANE Select	c.700C>T	p.Arg234Cys	missense	Exon 4 of 8	ENSP00000341787.6	Q6UXE8-1
	BTNL3	ENST00000899564.1		c.700C>T	p.Arg234Cys	missense	Exon 4 of 8	ENSP00000569623.1
	BTNL3	ENST00000946317.1		c.352C>T	p.Arg118Cys	missense	Exon 3 of 7	ENSP00000616376.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1323986 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 660258

African (AFR) AF: 0.00 AC: 0 AN: 32842

American (AMR) AF: 0.00 AC: 0 AN: 40322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25056

East Asian (EAS) AF: 0.00 AC: 0 AN: 36160

South Asian (SAS) AF: 0.00 AC: 0 AN: 84658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 997346

Other (OTH) AF: 0.0000181 AC: 1 AN: 55260

GnomAD4 genome Cov.: 21

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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.6
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N
PhyloP100		-1.6
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.075
Sift	Benign	0.068	T
Sift4G	Benign	0.18	T
Polyphen		0.97	D
Vest4		0.20
MutPred		0.56		Gain of catalytic residue at L235 (P = 0.0112)
MVP		0.37
MPC		1.0
ClinPred		0.36	T
GERP RS		-2.9
Varity_R		0.089
gMVP		0.15
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1760145027; hg19: chr5-180429698;