5-181045589-C-T

Variant names:

• chr5-181045589-C-T
• NM_152547.5:c.100C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152547.5(BTNL9):​c.100C>T​(p.Pro34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTNL9 NM_152547.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0910

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0444237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL9	NM_152547.5	c.100C>T	p.Pro34Ser	missense_variant	Exon 2 of 11	ENST00000327705.14	NP_689760.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL9	ENST00000327705.14	c.100C>T	p.Pro34Ser	missense_variant	Exon 2 of 11	1	NM_152547.5	ENSP00000330200.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459036 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100C>T (p.P34S) alteration is located in exon 2 (coding exon 1) of the BTNL9 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the proline (P) at amino acid position 34 to be replaced by a serine (S). 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	0.078
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.95
DANN	Benign	0.76
DEOGEN2	Benign	0.015	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.15	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.010
Sift	Benign	0.50	T;T
Sift4G	Benign	0.071	T;T
Polyphen		0.0010	.;B
Vest4		0.10
MutPred		0.24		Gain of phosphorylation at P34 (P = 0.0412);Gain of phosphorylation at P34 (P = 0.0412);
MVP		0.24
MPC		0.26
ClinPred		0.065	T
GERP RS		-0.65
Varity_R		0.024
gMVP		0.089

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-180472589;