3-119544709-A-G

Position:

• chr3-119544709-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005191.4(CD80):​c.259T>C​(p.Tyr87His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD80 NM_005191.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

CD80 (HGNC:1700): (CD80 molecule) The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. The activated protein induces T-cell proliferation and cytokine production. This protein can act as a receptor for adenovirus subgroup B and may play a role in lupus neuropathy. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD80	NM_005191.4	c.259T>C	p.Tyr87His	missense_variant	3/7	ENST00000264246.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD80	ENST00000264246.8	c.259T>C	p.Tyr87His	missense_variant	3/7	1	NM_005191.4	P2
CD80	ENST00000478182.5	c.259T>C	p.Tyr87His	missense_variant	3/6	1		P2
CD80	ENST00000383669.3	c.259T>C	p.Tyr87His	missense_variant	2/4	1		A2
CD80	ENST00000463729.1	n.371T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 20, 2023

The c.259T>C (p.Y87H) alteration is located in exon 3 (coding exon 2) of the CD80 gene. This alteration results from a T to C substitution at nucleotide position 259, causing the tyrosine (Y) at amino acid position 87 to be replaced by a histidine (H). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D;D;.
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Pathogenic	3.1	M;M;M
MutationTaster	Benign	0.92	N;N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.55
MutPred		0.74		Gain of methylation at K88 (P = 0.0751);Gain of methylation at K88 (P = 0.0751);Gain of methylation at K88 (P = 0.0751);
MVP		0.88
MPC		0.77
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.87

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: chr3-119263556;