chr3-112466176-T-A

Position:

• chr3-112466176-T-A

Variant summary

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

The NM_181780.4(BTLA):​c.802A>T​(p.Asn268Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BTLA NM_181780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

Genes affected

BTLA (HGNC:21087): (B and T lymphocyte associated) This gene encodes a member of the immunoglobulin superfamily. The encoded protein contains a single immunoglobulin (Ig) domain and is a receptor that relays inhibitory signals to suppress the immune response. Alternative splicing results in multiple transcript variants. Polymorphisms in this gene have been associated with an increased risk of rheumatoid arthritis. [provided by RefSeq, Aug 2011]

BTLA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTLA	NM_181780.4	c.802A>T	p.Asn268Tyr	missense_variant	5/5	ENST00000334529.10	NP_861445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTLA	ENST00000334529.10	c.802A>T	p.Asn268Tyr	missense_variant	5/5	1	NM_181780.4	ENSP00000333919.5
BTLA	ENST00000383680.4	c.658A>T	p.Asn220Tyr	missense_variant	4/4	1		ENSP00000373178.4
BTLA	ENST00000474965.1	n.306A>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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 21, 2023

The c.802A>T (p.N268Y) alteration is located in exon 5 (coding exon 5) of the BTLA gene. This alteration results from a A to T substitution at nucleotide position 802, causing the asparagine (N) at amino acid position 268 to be replaced by a tyrosine (Y). 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	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.53	D;.
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.36
MutPred		0.37		Gain of catalytic residue at N268 (P = 0.0237);.;
MVP		0.76
MPC		1.8
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.069
gMVP		0.22

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: chr3-112185023;