5-181048242-G-C

Variant names:

• chr5-181048242-G-C
• NM_152547.5:c.425G>C

Variant summary

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

The NM_152547.5(BTNL9):​c.425G>C​(p.Gly142Ala) 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: 31)
• Consequence: BTNL9 NM_152547.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180

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]

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=0.19797167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL9	NM_152547.5	c.425G>C	p.Gly142Ala	missense_variant	Exon 3 of 11	ENST00000327705.14	NP_689760.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL9	ENST00000327705.14	c.425G>C	p.Gly142Ala	missense_variant	Exon 3 of 11	1	NM_152547.5	ENSP00000330200.9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.425G>C (p.G142A) alteration is located in exon 3 (coding exon 2) of the BTNL9 gene. This alteration results from a G to C substitution at nucleotide position 425, causing the glycine (G) at amino acid position 142 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.8
DANN	Benign	0.95
DEOGEN2	Benign	0.036	.;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.4	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.10, 0.96	.;B;D
Vest4		0.15
MutPred		0.77		Loss of glycosylation at S141 (P = 0.0554);Loss of glycosylation at S141 (P = 0.0554);.;
MVP		0.23
MPC		0.34
ClinPred		0.22	T
GERP RS		1.3
Varity_R		0.086
gMVP		0.23

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: chr5-180475242;